A Clinical Study Using MEDI-551 in Adult Participants With Relapsed or Refractory Advanced B-Cell Malignancies

• Sponsor: MedImmune LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00983619
• Collaborator: (none)
• Enrollment: 136
• Locations: 21
• Arms: 12
• Actual Duration (Months): 107.1
• Patients Per Site: 6.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the maximum tolerated dose of this drug (MEDI-551) in participants with advanced B-cell malignancies. Expansion to occur at maximum tolerated dose (MTD), or if not reached, at optimal biologic dose (OBD).

Condition or Disease	Intervention/Treatment	Phase
B-cell Malignancies; Cancer	Drug: MEDI-551; Drug: Rituximab	Phase 1/Phase 2

Detailed Description

To determine the MTD or OBD of MEDI-551 in participants with relapsed or refractory advanced B-cell malignancies.

Study Design

• Study Type: Interventional
• Actual Enrollment: 136 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Dose-escalation Study of MEDI-551, a Humanized Monoclonal Antibody Directed Against CD19, in Adult Subjects With Relapsed or Refractory Advanced B-Cell Malignancies
• Actual Study Start Date: Apr 16, 2010
• Actual Primary Completion Date: Mar 21, 2019
• Actual Study Completion Date: Mar 21, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A-MEDI-551 0.5 mg/kg Participants will receive intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.	Drug: MEDI-551; MEDI-551 will be administered intravenously (IV) once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.
Experimental: Part A-MEDI-551 1 mg/kg Participants will receive IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.	Drug: MEDI-551; MEDI-551 will be administered intravenously (IV) once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.
Experimental: Part A-MEDI-551 2 mg/kg Participants will receive IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.	Drug: MEDI-551; MEDI-551 will be administered intravenously (IV) once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.
Experimental: Part A-MEDI-551 4 mg/kg Participants will receive IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.	Drug: MEDI-551; MEDI-551 will be administered intravenously (IV) once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.
Experimental: Part A-MEDI-551 8 mg/kg Participants will receive IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.	Drug: MEDI-551; MEDI-551 will be administered intravenously (IV) once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.
Experimental: Part A-MEDI-551 12 mg/kg Participants will receive IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.	Drug: MEDI-551; MEDI-551 will be administered intravenously (IV) once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.
Experimental: Part B-MEDI-551 6 mg/kg Participants will receive IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.	Drug: MEDI-551; MEDI-551 will be administered intravenously (IV) once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.
Experimental: Part B-MEDI-551 12 mg/kg Participants will receive IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.	Drug: MEDI-551; MEDI-551 will be administered intravenously (IV) once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.
Experimental: Part B-MEDI-551 24 mg/kg Participants will receive IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.	Drug: MEDI-551; MEDI-551 will be administered intravenously (IV) once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.
Experimental: Part C-MEDI-551 8 mg/kg + rituximab Participants will receive IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg will be administered on Day 1 of each 28-day cycle. The treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches complete response or withdraws consent.	Drug: MEDI-551; MEDI-551 will be administered intravenously (IV) once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.; Drug: Rituximab; Rituximab will be administered IV on Days 1, 8, 15, and 22 (28- day cycle). The treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches complete response or withdraws consent.
Experimental: Part C-MEDI-551 12 mg/kg + rituximab Participants will receive IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg will be administered on Day 1 of each 28-day cycle. The treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches complete response or withdraws consent.	Drug: MEDI-551; MEDI-551 will be administered intravenously (IV) once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.; Drug: Rituximab; Rituximab will be administered IV on Days 1, 8, 15, and 22 (28- day cycle). The treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches complete response or withdraws consent.
Experimental: Part D-MEDI-551 12 mg/kg Participants will receive IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches CR or withdraws consent.	Drug: MEDI-551; MEDI-551 will be administered intravenously (IV) once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Outcome Measures

Primary Outcome Measures

1. Optimal Biologic Dose of MEDI-551 for Part A [Day 1 to Day 28 of Cycle 1]

   Optimal biologic dose (OBD) was defined as the dose lower than the maximum tolerated dose (MTD), used for dose expansion. The MTD is defined as the highest dose at which less than equal to (<=) 1 out of 6 participants experience a dose limiting toxicities (DLT) from the time of first administration of MEDI-551 through the first 28-day cycle.

2. Highest Protocol-defined Dose for Part B [Day 1 to Day 28 of Cycle 1]

   Highest protocol-defined dose is dose of MEDI-551 in the absence of exceeding the MTD in participants with relapsed or rituximab-refractory chronic lymphocytic leukemia (defined as those with less than a partial response (PR) or progression within 6 months after completing therapy with rituximab). The MTD is defined as the highest dose at which <= 1 out of 6 participants experience a DLT from the time of first administration of MEDI-551 through the first 28-day cycle.

3. Highest Protocol-defined Dose for Part C [Day 1 to Day 28 of Cycle 1]

   Highest protocol-defined dose is the dose of MEDI-551 in combination with rituximab at the MTD or the highest protocol-defined dose in the absence of exceeding the MTD in participants with aggressive lymphomas. The MTD is defined as the highest dose at which <= 1 out of 6 participants experience a DLT from the time of first administration of MEDI-551 through the first 28-day cycle.

4. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Part A, Part B, and Part C [Day 1 through 90-Day Post Last Dose (Approximately 9 years)]

   An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

5. Number of Participants With Dose Limiting Toxicities of MEDI-551 in Part A, Part B, and Part C [Day 1 to Day 28 of Cycle 1]

   A dose limiting toxicities (DLT) for arm A, B, and C was defined as MEDI-551 (or rituximab for Arm C) treatment-related AE of any toxicity grade that led to an inability to receive a full cycle of MEDI-551 (or rituximab for Arm C) or any Grade 3 or higher toxicity (except Grade 3 fever, transient Grade 3 rigors or chills, Grade 3 tumor lysis syndrome, any Grade 3 or 4 electrolyte alteration, any Grade 3 liver function test elevation,>= Grade 3 or 4 lymphopenia or leukopenia, <= Grade 4 neutropenia, <= Grade 4 thrombocytopenia, <= Grade 4 anemia, and Grade 3 infusion-related reaction and infusion reaction), during DLT evaluable period.

6. Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part A, Part B, and Part C [Day 1 through 90-Day Post Last Dose (Approximately 9 years)]

   Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urine.

7. Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part A, Part B, and Part C [Day 1 through 90-Day Post Last Dose (Approximately 9 years)]

   Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital signs parameters (temperature, blood pressure, pulse rate, respiratory rate, and pulse oximetry).

8. Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part A, Part B, and Part C [Day 1 through 90-Day Post Last Dose (Approximately 9 years)]

   Number of participants with abnormal electrocardiograms (ECGs) reported as TEAEs are reported. Abnormal ECGs are defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, axis, and QT intervals from the primary lead of the digital 12-lead ECG.

9. Percentage of Participants With Complete Response for Part B, Part C, and Part D [Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

   Complete response (CR) is defined as disappearance of all evidence of disease according to International Working Group criteria (IWG). For nodal masses; fluorodeoxyglucose (FDG)-avid or polyethylene terephthalate (PET) positive prior to therapy; mass of any size permitted if PET negative .Variably FDG-avid or PET negative; regression to normal size on computed tomography (CT). For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry (IHC) was negative.

10. Percentage of Participants With Partial Response for Part B, Part C, and Part D [Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

    The PR is defined as regression of measurable disease and no new sites according to IWG criteria. Nodal masses: >= 50% decrease in sum of the product diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. Spleen and liver: >= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone marrow: irrelevant if positive prior to therapy.

11. Duration of Complete Response for Part B, Part C, and Part D [Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

    Duration of CR is from the first documentation of a CR to the time of progressive disease/relapse according to IWG criteria. The CR is disappearance of all evidence of disease according to IWG criteria. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. Variably FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. Kaplan-Meier method was used to evaluate duration of CR.

12. Percentage of Participants With Objective Response Rate for Part B, Part C, and Part D [Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

    Objective response rate (ORR) is proportion of participants with CR or partial response (PR) as per IWG criteria. CR is disappearance of all evidence of disease. Nodal masses; FDG-avid/PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. Spleen; not palpable, nodules disappeared. Bone marrow; infiltrate cleared on repeat biopsy; if unknown by morphology, IHC was negative. PR is regression of measurable disease and no new sites. Nodal masses: >= 50% decrease in sum of the product diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. Spleen and liver: >= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone marrow: irrelevant if positive prior to therapy.

13. Duration of Objective Response for Part B, Part C, and Part D [Cycle 1 Day 1, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

    Duration of objective response (DOR) is the first documentation of objective response to the first documented progressive disease (PD) or relapse according to IWG criteria. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) > 1.5 cm in any axis, >= 50% increase in SPD of more than one node, or >= 50% increase in longest diameter of a previously identified node > 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: > 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate DOR.

14. Percentage of Participants With Disease Control Rate for Part B, Part C, and Part D [Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

    Disease control includes CR, PR, or stable disease (SD) for at least 8 weeks according to IWG criteria. The CR is disappearance of all evidence of disease. Nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. Spleen; not palpable, nodules disappeared. Bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. PR is regression of measurable disease and no new sites. Nodal masses: >= 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) Variably FDG-avid or PET negative; regression on CT. Spleen and liver: >= 50% decrease in SPD of nodules; no increase in size of liver or spleen. For bone marrow: irrelevant if positive prior to therapy. SD is failure to attain CR/PR or PD.

15. Duration of Disease Control for Part B, Part C, and Part D [Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

    Duration of disease control is defined as the time period from start of MEDI-551 administration to the event of PD/relapse. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) > 1.5 cm in any axis, >= 50% increase in SPD of more than one node, or >= 50% increase in longest diameter of a previously identified node > 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: > 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate duration of disease control.

16. Time to Response for Part B, Part C, and Part D [Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

    Time to response (TTR) is measured from the start of MEDI-551 administration to the first documentation of response (CR or PR) and assessed in participants who have achieved objective response. Kaplan-Meier method was used to evaluate TTR.

17. Progression Free Survival for Part B, Part C, and Part D [Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

    Progression-free survival (PFS) is measured from the start of MEDI-551 treatment until the first documentation of disease progression, relapse or death, whichever occurs first. The PFS was censored on the date of last disease assessment for participants who have no documented PD/relapse or death prior to data cutoff, dropout, or the initiation of alternative anticancer therapy. Kaplan-Meier method was used to evaluate PFS.

18. Overall Survival for Part B, Part C, and Part D [Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

    Overall survival (OS) is measured from the start of MEDI-551 treatment until death. For participants who are alive at the end of study or lost to follow-up, OS will be censored on the last date when participants were known to be alive. Kaplan-Meier method was used to evaluate OS.

Secondary Outcome Measures

1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Part D [Day 1 through 90-Day Post Last Dose (Approximately 9 years)]

   An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

2. Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part D [Day 1 through 90-Day Post Last Dose (Approximately 9 years)]

   Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urine.

3. Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part D [Day 1 through 90-Day Post Last Dose (Approximately 9 years)]

   Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital signs parameters (temperature, blood pressure, pulse rate, respiratory rate, and pulse oximetry).

4. Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part D [Day 1 through 90-Day Post Last Dose (Approximately 9 years)]

   Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs are defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, axis, and QT intervals from the primary lead of the digital 12-lead ECG.

5. Percentage of Participants With Complete Response for Part A [Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

   The CR is defined as disappearance of all evidence of disease according to IWG criteria. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative .Variably FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative.

6. Percentage of Participants With Partial Response for Part A [Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

   The PR is defined as regression of measurable disease and no new sites according to IWG criteria. Nodal masses: >= 50% decrease in sum of the product diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. Spleen and liver: >= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone marrow: irrelevant if positive prior to therapy.

7. Duration of Complete Response for Part A [Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

   Duration of CR is from the first documentation of a CR to the time of progressive disease/relapse according to IWG criteria. The CR is disappearance of all evidence of disease. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. Variably FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. Kaplan-Meier method was used to evaluate duration of CR.

8. Percentage of Participants With Objective Response Rate for Part A [Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

   The ORR is defined as proportion of participants with CR or PR according to IWG criteria. CR is disappearance of all evidence of disease. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if unknown by morphology, IHC was negative. PR is regression of measurable disease and no new sites. For nodal masses: >= 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. For spleen and liver: >= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. For bone marrow: irrelevant if positive prior to therapy.

9. Duration of Objective Response for Part A [Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

   The DOR is the first documentation of objective response to the first documented PD or relapse according to IWG criteria. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) > 1.5 cm in any axis, >= 50% increase in SPD of more than one node, or >= 50% increase in longest diameter of a previously identified node > 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: > 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate DOR.

10. Percentage of Participants With Disease Control Rate for Part A [Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

    Disease control includes CR, PR, or SD for at least 8 weeks according to IWG criteria. The CR is disappearance of all evidence of disease. For nodal masses; FDG -avid or PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. PR is regression of measurable disease and no new sites. For nodal masses: >= 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) Variably FDG-avid or PET negative; regression on CT. For spleen and liver: >= 50% decrease in SPD of nodules; no increase in size of liver or spleen. For bone marrow: irrelevant if positive prior to therapy. SD is failure to attain CR/PR or PD.

11. Duration of Disease Control for Part A [Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

    Duration of disease control is defined as the time period from start of MEDI-551 administration to the event of PD/relapse according to IWG criteria. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) > 1.5 cm in any axis, >= 50% increase in SPD of more than one node, or >= 50% increase in longest diameter of a previously identified node > 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: > 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate duration of disease control.

12. Time to Response for Part A [Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

    The TTR is measured from the start of MEDI-551 administration to the first documentation of response (CR or PR) and assessed in participants who have achieved objective response. Kaplan-Meier method was used to evaluate TTR.

13. Progression Free Survival for Part A [Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

    The PFS is measured from the start of MEDI-551 treatment until the first documentation of disease progression, relapse or death, whichever occurs first. Kaplan-Meier method was used to evaluate PFS. The PFS was censored on the date of last disease assessment for participants who have no documented PD/relapse or death prior to data cutoff, dropout, or the initiation of alternative anticancer therapy.

14. Overall Survival for Part A [Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)]

    The OS is measured from the start of MEDI-551 treatment until death. For participants who are alive at the end of study or lost to follow-up, OS will be censored on the last date when participants were known to be alive. Kaplan-Meier method was used to evaluate OS.

15. Trough Serum Concentration of MEDI-551 by Treatment Cycle [For Part A: C1D1 of each cycles; For Part B: C1D1 of each cycle + C1D8, C1D15, and C1D22; For Part C: C1D2, C1D8, then Day 1 of each cycle until Cycle 10;For Part D: C1D1, C1D8, then Day 1 of each cycle until Cycle 10]

    Trough serum concentration (Ctrough) is defined as lowest concentration reached by a drug before the next dose is administered. The Ctrough concentration of MEDI-551 by treatment cycle is reported.

16. Peak Serum Concentration of MEDI-551 by Treatment Cycle [For Part A: C1D1 of each cycles; For Part B: C1D1 of each cycle + C1D8, C1D15, and C1D22; For Part C: C1D2, C1D8, then Day 1 of each cycle until Cycle 10;For Part D: C1D1, C1D8, then Day 1 of each cycle until Cycle 10]

    Peak serum concentration is concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and before the administration of a second dose.

17. Area Under the Concentration Curve at Steady State (AUCss) of MEDI-551 [Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24]

    Area under the concentration-time curve at steady state (Css, AUC) of MEDI-551 is reported.

18. Apparent Clearance of MEDI-551 [Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24]

    Apparent clearance of MEDI-551 is reported.

19. Volume of Distribution of MEDI-551 [Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24]

    Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Central volume of distribution (Vd1) is defined as hypothetical volume into which a drug initially distributes upon administration and peripheral volume of distribution (Vd2) is defined as the sum of all tissue spaces outside the central compartment.

20. Terminal Half-life (t1/2) of MEDI-551 [Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24]

    Terminal half-life is the time required for the plasma concentration of MEDI-551 to fall by 50% during the terminal phase.

21. Number of Participants With Positive Anti-drug Antibodies (ADA) Titer to MEDI-551 [Part A:C1D1; Part B: C1D1; Part C: C1D1; Part D: C1D1; End of treatment (EOT); 90 Days post last dose (approximately 9 years)]

    Number of participants with positive Anti-drug antibodies (ADA) titer to MEDI-551 is reported.

22. B-cell Concentration in Serum [Part A:C1D1 of each cycles; Part B: C1D1 of each cycle + C1D8, C1D15, and C1D22; Part C: C1D2, C1D8, then Day 1 of each cycle until Cycle 10; Part D: C1D1, C1D8, Day 1 of each cycle until Cycle 10; EOT;90 Days post last dose (approximately 9 years)]

    B-cell Concentration in serum is reported.

23. Immunoglobulin (Ig) Concentration in Serum [Part A:C1D1 of each cycles; EOT;90 Days post last dose (approximately 9 years)]

    Immunoglobin (Ig) concentration in serum is reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed CLL, DLBCL, FL, or MM;

• Karnofsky Performance Status >= 70;

• Life expectancy of >= 12 weeks;

• Prior radiation therapy provided exposure does not exceed an area of 25% of marrow space

• Adequate hematological function

• Adequate organ function

Exclusion Criteria:

• Any available standard line of therapy known to be life-prolonging or life-saving;

• No concurrent therapy or therapy within six weeks of first dose of MEDI-551 for treatment of cancer

• Previous therapy directed against CD19

• Vaccination (other than experimental cancer vaccine therapy) within 28 days prior to receiving the first dose of MEDI-551;

• History of other invasive malignancy within 5 years except for cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured;

• Active infection requiring treatment

• Autologous stem cell transplantation within 4 months prior to study entry;

• Allogeneic stem cell transplantation or any other organ transplant;

• Ongoing >= Grade 2 toxicities from previous cancer therapies unless specifically allowed in the Inclusion/Exclusion criteria.

• Use of immunosuppressive medication other than steroids within 28 days before the first dose of MEDI-551;

• Use of immunosuppressive medication other than steroids within 28 days before the first dose of MEDI-551 (inhaled and topical corticosteroids are permitted);

• Documented current central nervous system involvement by leukemia or lymphoma;

• Pregnancy or lactation;

• Clinically significant abnormality on ECG.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35249
2	Research Site	La Jolla	California	United States	92093
3	Research Site	Washington	District of Columbia	United States	20007
4	Research Site	Tampa	Florida	United States	33612
5	Research Site	Chicago	Illinois	United States	60612
6	Research Site	Westwood	Kansas	United States	66205
7	Research Site	Rochester	Minnesota	United States	55905
8	Research Site	New Brunswick	New Jersey	United States	08903
9	Research Site	Lake Success	New York	United States	11042
10	Research Site	Hershey	Pennsylvania	United States	17033
11	Research Site	Houston	Texas	United States	77030
12	Research Site	Morgantown	West Virginia	United States	26506
13	Research Site	Milwaukee	Wisconsin	United States	53226
14	Research Site	Gent		Belgium	9000
15	Research Site	Leuven		Belgium	3000
16	Research Site	Yvoir		Belgium	5530
17	Research Site	Montreal	Quebec	Canada	H3T 1E2
18	Research Site	Cona		Italy	44124
19	Research Site	Modena		Italy	41124
20	Research Site	Madrid		Spain	28033
21	Research Site	Madrid		Spain	28050

Sponsors and Collaborators

• MedImmune LLC

Investigators

• Study Director: Medimmune Inc. Clinical Development, MedImmune LLC

Study Documents (Full-Text)

• Statistical Analysis Plan - Dec 3, 2015
• Study Protocol - Jun 1, 2017

More Information

Additional Information:

• Click here and search for drug information provided by the FDA.
• Click here to find results for studies related to marketed products.
• Statistical Analysis Plan (SAP)
• MI-CP204 redacted CSP

Publications

None provided.

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT00983619
• Other Study ID Numbers: MI-CP204; 2009-016378-34
• First Posted: Sep 24, 2009
• Last Update Posted: May 13, 2020
• Last Verified: Apr 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by MedImmune LLC: Cancer
• Additional relevant MeSH terms: Neoplasms; Rituximab

Study Results

Participant Flow

Pre-assignment Detail	A total of 137 participants were screened, out of which 1 participant never received the study treatment. A total of 136 participants received study treatment.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Period Title: Overall Study
STARTED	3	4	3	6	3	76	3	3	1	3	17	14
COMPLETED	0	0	0	1	0	9	0	1	0	0	6	3
NOT COMPLETED	3	4	3	5	3	67	3	2	1	3	11	11

Baseline Characteristics

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg	TOTAL
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.	Total of all reporting groups
Overall Participants	3	4	3	6	3	76	3	3	1	3	17	14	136
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	66.0 (19.5)	69.5 (12.5)	64.7 (18.3)	63.8 (12.7)	60.0 (12.1)	64.4 (11.2)	61.3 (20.8)	70.0 (7.0)	78.0 (NA)	68.0 (11.8)	69.4 (10.8)	67.9 (11.0)	65.7 (11.5)
Sex: Female, Male (Count of Participants)
Female	2 66.7%	0 0%	1 33.3%	2 33.3%	1 33.3%	30 39.5%	1 33.3%	1 33.3%	1 100%	1 33.3%	10 58.8%	5 35.7%	55 40.4%
Male	1 33.3%	4 100%	2 66.7%	4 66.7%	2 66.7%	46 60.5%	2 66.7%	2 66.7%	0 0%	2 66.7%	7 41.2%	9 64.3%	81 59.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%	6 7.9%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	6 4.4%
Not Hispanic or Latino	3 100%	4 100%	3 100%	6 100%	3 100%	70 92.1%	3 100%	3 100%	1 100%	3 100%	17 100%	14 100%	130 95.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 5.9%	0 0%	1 0.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 25%	0 0%	1 16.7%	0 0%	5 6.6%	0 0%	1 33.3%	0 0%	0 0%	0 0%	0 0%	8 5.9%
White	3 100%	3 75%	3 100%	5 83.3%	3 100%	68 89.5%	3 100%	2 66.7%	1 100%	2 66.7%	15 88.2%	14 100%	122 89.7%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	3 3.9%	0 0%	0 0%	0 0%	1 33.3%	1 5.9%	0 0%	5 3.7%

Outcome Measures

1. Primary Outcome

Title	Optimal Biologic Dose of MEDI-551 for Part A
Description	Optimal biologic dose (OBD) was defined as the dose lower than the maximum tolerated dose (MTD), used for dose expansion. The MTD is defined as the highest dose at which less than equal to (<=) 1 out of 6 participants experience a dose limiting toxicities (DLT) from the time of first administration of MEDI-551 through the first 28-day cycle.
Time Frame	Day 1 to Day 28 of Cycle 1

Outcome Measure Data

Analysis Population Description

Dose limiting toxicity evaluable population included all participants in the dose-escalation phase who received at least 1 full cycle of MEDI-551 and completed safety follow-up through the DLT evaluable period (from the time of first administration of MEDI-551 through the first 28-day of cycle 1).

Arm/Group Title	Part A-MEDI-551 Part A
Arm/Group Description	Participants received IV infusion of MEDI 551 0.5 or 1 mg/kg (both, once every week in 4-week cycles), or 2, or 4, or 8, or 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
Measure Participants	95
Number [mg/Kg]	12

2. Primary Outcome

Title	Highest Protocol-defined Dose for Part B
Description	Highest protocol-defined dose is dose of MEDI-551 in the absence of exceeding the MTD in participants with relapsed or rituximab-refractory chronic lymphocytic leukemia (defined as those with less than a partial response (PR) or progression within 6 months after completing therapy with rituximab). The MTD is defined as the highest dose at which <= 1 out of 6 participants experience a DLT from the time of first administration of MEDI-551 through the first 28-day cycle.
Time Frame	Day 1 to Day 28 of Cycle 1

Outcome Measure Data

Analysis Population Description

DLT evaluable population included all participants in the dose-escalation phase who received at least 1 full cycle of MEDI-551 and completed safety follow-up through the DLT evaluable period (from the time of first administration of MEDI-551 through the first 28-day of cycle).

Arm/Group Title	Part B-MEDI-551
Arm/Group Description	Participants received IV infusion of MEDI- 551 6 or 12 mg/kg weekly for 4 weeks during Cycle 1 (both from Days 1, 8, 15, and 22) or 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
Measure Participants	7
Number [mg/Kg]	24

3. Primary Outcome

Title	Highest Protocol-defined Dose for Part C
Description	Highest protocol-defined dose is the dose of MEDI-551 in combination with rituximab at the MTD or the highest protocol-defined dose in the absence of exceeding the MTD in participants with aggressive lymphomas. The MTD is defined as the highest dose at which <= 1 out of 6 participants experience a DLT from the time of first administration of MEDI-551 through the first 28-day cycle.
Time Frame	Day 1 to Day 28 of Cycle 1

Outcome Measure Data

Analysis Population Description

DLT evaluable population included all participants in the dose-escalation phase who received at least 1 full cycle of MEDI-551 and completed safety follow-up through the DLT evaluable period (from the time of first administration of MEDI-551 through the first 28-day of cycle 1).

Arm/Group Title	Part C-MEDI-551 + Rituximab
Arm/Group Description	Participants received IV infusion of MEDI- 551 8 or 12 mg/kg on days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 or 12 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdraws consent.
Measure Participants	20
Number [mg/kg]	12

4. Primary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Part A, Part B, and Part C
Description	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Time Frame	Day 1 through 90-Day Post Last Dose (Approximately 9 years)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any treatment of MEDI-551.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.
Measure Participants	3	4	3	6	3	76	3	3	1	3	17
TEAEs	3 100%	4 100%	3 100%	6 100%	3 100%	76 100%	3 100%	3 100%	1 100%	3 100%	17 100%
TESAEs	1 33.3%	1 25%	2 66.7%	1 16.7%	1 33.3%	23 30.3%	1 33.3%	2 66.7%	1 100%	1 33.3%	9 52.9%

5. Primary Outcome

Title	Number of Participants With Dose Limiting Toxicities of MEDI-551 in Part A, Part B, and Part C
Description	A dose limiting toxicities (DLT) for arm A, B, and C was defined as MEDI-551 (or rituximab for Arm C) treatment-related AE of any toxicity grade that led to an inability to receive a full cycle of MEDI-551 (or rituximab for Arm C) or any Grade 3 or higher toxicity (except Grade 3 fever, transient Grade 3 rigors or chills, Grade 3 tumor lysis syndrome, any Grade 3 or 4 electrolyte alteration, any Grade 3 liver function test elevation,>= Grade 3 or 4 lymphopenia or leukopenia, <= Grade 4 neutropenia, <= Grade 4 thrombocytopenia, <= Grade 4 anemia, and Grade 3 infusion-related reaction and infusion reaction), during DLT evaluable period.
Time Frame	Day 1 to Day 28 of Cycle 1

Outcome Measure Data

Analysis Population Description

DLT evaluable population included all participants in the dose-escalation phase who received at least 1 full cycle of MEDI-551 and completed safety follow-up through the DLT evaluable period (from the time of first administration of MEDI-551 through the first 28-day of cycle 1).

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.
Measure Participants	3	4	3	6	3	76	3	3	1	3	17
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	0 0%	0 0%	0 0%	0 0%	0 0%

6. Primary Outcome

Title	Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part A, Part B, and Part C
Description	Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urine.
Time Frame	Day 1 through 90-Day Post Last Dose (Approximately 9 years)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any treatment of MEDI-551.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.
Measure Participants	3	4	3	6	3	76	3	3	1	3	17
Anemia	0 0%	2 50%	0 0%	0 0%	1 33.3%	6 7.9%	0 0%	1 33.3%	1 100%	0 0%	4 23.5%
Blood fibrinogen decreased	0 0%	1 25%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	0 0%
Blood fibrinogen increased	0 0%	1 25%	0 0%	0 0%	0 0%	1 1.3%	0 0%	1 33.3%	0 0%	0 0%	0 0%
Febrile neutropenia	0 0%	0 0%	0 0%	0 0%	0 0%	2 2.6%	0 0%	1 33.3%	0 0%	0 0%	1 5.9%
Hematocrit decreased	0 0%	1 25%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Hemoglobin increased	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	0 0%	0 0%	0 0%	0 0%	0 0%
Leukopenia	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	0 0%	1 33.3%	0 0%	0 0%	0 0%
Lymphocyte count decreased	0 0%	1 25%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 100%	0 0%	2 11.8%
Lymphopenia	0 0%	0 0%	0 0%	0 0%	0 0%	2 2.6%	0 0%	1 33.3%	0 0%	0 0%	0 0%
Myelocytosis	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	0 0%	0 0%	0 0%	0 0%	0 0%
Neutropenia	0 0%	0 0%	0 0%	1 16.7%	1 33.3%	14 18.4%	1 33.3%	1 33.3%	0 0%	1 33.3%	2 11.8%
Neutrophil count abnormal	0 0%	1 25%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Neutrophil count decreased	1 33.3%	1 25%	0 0%	1 16.7%	0 0%	5 6.6%	0 0%	1 33.3%	1 100%	0 0%	2 11.8%
Platelet count decreased	0 0%	0 0%	0 0%	0 0%	0 0%	2 2.6%	0 0%	1 33.3%	1 100%	0 0%	1 5.9%
Red blood cell count decreased	0 0%	1 25%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Reticulocytosis	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	0 0%	0 0%	0 0%	0 0%	0 0%
Thrombocytopenia	0 0%	1 25%	0 0%	3 50%	0 0%	6 7.9%	0 0%	1 33.3%	0 0%	0 0%	2 11.8%
White blood cell count decreased	0 0%	0 0%	0 0%	1 16.7%	1 33.3%	3 3.9%	0 0%	2 66.7%	1 100%	0 0%	2 11.8%
Hypergammaglobulinemia	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	0 0%	0 0%
Activated PTT prolonged	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 5.9%
Leukocytosis	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 5.9%
Alanine aminotransferase increased	0 0%	1 25%	0 0%	0 0%	0 0%	3 3.9%	0 0%	0 0%	1 100%	0 0%	1 5.9%
Aspartate aminotransferase increased	0 0%	1 25%	0 0%	0 0%	0 0%	4 5.3%	0 0%	0 0%	1 100%	0 0%	1 5.9%
Blood alkaline phosphatase increased	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	0 0%	0 0%	1 100%	0 0%	2 11.8%
Blood chloride decreased	0 0%	1 25%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Blood creatinine increased	0 0%	0 0%	1 33.3%	0 0%	0 0%	1 1.3%	0 0%	1 33.3%	1 100%	0 0%	2 11.8%
Blood glucose decreased	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	0 0%	0 0%	0 0%	0 0%	0 0%
Blood glucose increased	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	0 0%	0 0%	0 0%	0 0%	0 0%
Blood lactate dehydrogenase increased	0 0%	0 0%	0 0%	0 0%	0 0%	2 2.6%	0 0%	0 0%	1 100%	0 0%	1 5.9%
Blood potassium decreased	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	0 0%	0 0%	0 0%	0 0%	0 0%
Blood urea increased	0 0%	1 25%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Blood uric acid increased	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	0 0%	0 0%	0 0%	0 0%	0 0%
Gamma-glutamyl transferase increased	0 0%	0 0%	0 0%	0 0%	0 0%	3 3.9%	0 0%	0 0%	0 0%	0 0%	0 0%
Hyperbilirubinemia	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 5.9%
Hypercalcemia	0 0%	0 0%	0 0%	0 0%	0 0%	4 5.3%	0 0%	0 0%	0 0%	0 0%	1 5.9%
Hyperglycemia	0 0%	0 0%	0 0%	1 16.7%	0 0%	1 1.3%	0 0%	0 0%	0 0%	0 0%	2 11.8%
Hyperkalemia	0 0%	2 50%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Hyperuricemia	1 33.3%	1 25%	0 0%	0 0%	0 0%	2 2.6%	0 0%	0 0%	1 100%	0 0%	1 5.9%
Hypocalcemia	0 0%	2 50%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	1 100%	0 0%	2 11.8%
Hypoglycemia	0 0%	1 25%	0 0%	0 0%	0 0%	1 1.3%	0 0%	0 0%	0 0%	0 0%	1 5.9%
Hypokalemia	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	0 0%	1 33.3%	0 0%	0 0%	1 5.9%
Hypomagnesemia	0 0%	0 0%	0 0%	0 0%	0 0%	2 2.6%	0 0%	1 33.3%	0 0%	0 0%	1 5.9%
Hyponatremia	0 0%	1 25%	0 0%	1 16.7%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	2 11.8%
Protein total decreased	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	0 0%
Blood albumin decreased	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	0 0%
Hypernatremia	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 100%	0 0%	2 11.8%
Hypoalbuminemia	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 100%	0 0%	2 11.8%
Haematuria	0 0%	0 0%	0 0%	0 0%	0 0%	2 2.6%	0 0%	0 0%	0 0%	0 0%	2 11.8%
Dysuria	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	0 0%	0 0%	0 0%	0 0%	2 11.8%
Pollakiuria	0 0%	0 0%	0 0%	0 0%	0 0%	2 2.6%	0 0%	0 0%	0 0%	0 0%	0 0%
Hemoglobinuria	0 0%	0 0%	0 0%	0 0%	0 0%	2 2.6%	0 0%	0 0%	0 0%	0 0%	0 0%
Hydronephrosis	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	2 11.8%
Urinary incontinence	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	0 0%	0 0%	0 0%	0 0%	1 5.9%

7. Primary Outcome

Title	Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part A, Part B, and Part C
Description	Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital signs parameters (temperature, blood pressure, pulse rate, respiratory rate, and pulse oximetry).
Time Frame	Day 1 through 90-Day Post Last Dose (Approximately 9 years)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any treatment of MEDI-551.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.
Measure Participants	3	4	3	6	3	76	3	3	1	3	17
Bradycardia	1 33.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Chills	0 0%	0 0%	0 0%	1 16.7%	0 0%	5 6.6%	0 0%	1 33.3%	0 0%	0 0%	1 5.9%
Dyspnea	0 0%	1 25%	1 33.3%	1 16.7%	0 0%	10 13.2%	0 0%	2 66.7%	1 100%	0 0%	4 23.5%
Hypertension	2 66.7%	1 25%	0 0%	0 0%	0 0%	8 10.5%	0 0%	2 66.7%	0 0%	0 0%	2 11.8%
Hypotension	1 33.3%	3 75%	1 33.3%	0 0%	0 0%	4 5.3%	0 0%	0 0%	1 100%	0 0%	2 11.8%
Orthostatic hypotension	0 0%	0 0%	1 33.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Palpitations	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	0 0%	0 0%	0 0%	0 0%	1 5.9%
Pyrexia	0 0%	0 0%	1 33.3%	2 33.3%	0 0%	16 21.1%	1 33.3%	1 33.3%	0 0%	0 0%	3 17.6%
Systolic hypertension	0 0%	0 0%	0 0%	0 0%	0 0%	2 2.6%	0 0%	0 0%	0 0%	0 0%	0 0%
Tachycardia	0 0%	0 0%	0 0%	0 0%	0 0%	6 7.9%	1 33.3%	0 0%	0 0%	0 0%	1 5.9%

8. Primary Outcome

Title	Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part A, Part B, and Part C
Description	Number of participants with abnormal electrocardiograms (ECGs) reported as TEAEs are reported. Abnormal ECGs are defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, axis, and QT intervals from the primary lead of the digital 12-lead ECG.
Time Frame	Day 1 through 90-Day Post Last Dose (Approximately 9 years)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any treatment of MEDI-551.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.
Measure Participants	3	4	3	6	3	76	3	3	1	3	17
Sinus bradycardia	0 0%	1 25%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Atrial fibrillation	0 0%	0 0%	0 0%	0 0%	0 0%	3 3.9%	0 0%	1 33.3%	0 0%	0 0%	0 0%
Mitral valve incompetence	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	0 0%	0 0%	0 0%	1 33.3%	0 0%
Supraventricular extrasystoles	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	0 0%	0 0%	0 0%	0 0%	0 0%
Tricuspid valve incompetence	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	0 0%	0 0%	0 0%	0 0%	0 0%
ECG QT prolonged	0 0%	0 0%	1 33.3%	0 0%	0 0%	1 1.3%	0 0%	0 0%	0 0%	0 0%	1 5.9%
Atrial flutter	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	0 0%
Atrial tachycardia	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	0 0%
Supraventricular tachycardia	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	1 5.9%

9. Primary Outcome

Title	Percentage of Participants With Complete Response for Part B, Part C, and Part D
Description	Complete response (CR) is defined as disappearance of all evidence of disease according to International Working Group criteria (IWG). For nodal masses; fluorodeoxyglucose (FDG)-avid or polyethylene terephthalate (PET) positive prior to therapy; mass of any size permitted if PET negative .Variably FDG-avid or PET negative; regression to normal size on computed tomography (CT). For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry (IHC) was negative.
Time Frame	Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment.

Arm/Group Title	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	3	3	0	3	16	13
Number (95% Confidence Interval) [Percentage of Participants]	33.3 1110%	0 0%	33.3 1110%	18.8 313.3%	0 0%

10. Primary Outcome

Title	Percentage of Participants With Partial Response for Part B, Part C, and Part D
Description	The PR is defined as regression of measurable disease and no new sites according to IWG criteria. Nodal masses: >= 50% decrease in sum of the product diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. Spleen and liver: >= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone marrow: irrelevant if positive prior to therapy.
Time Frame	Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment.

Arm/Group Title	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	3	3	0	3	16	13
Number [Percentage of Participants]	33.3 1110%	33.3 832.5%	33.3 1110%	25.0 416.7%	23.1 770%

11. Primary Outcome

Title	Duration of Complete Response for Part B, Part C, and Part D
Description	Duration of CR is from the first documentation of a CR to the time of progressive disease/relapse according to IWG criteria. The CR is disappearance of all evidence of disease according to IWG criteria. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. Variably FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. Kaplan-Meier method was used to evaluate duration of CR.
Time Frame	Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment. Duration of CR is calculated for participants with CR.

Arm/Group Title	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	1	0	0	1	3	0
Median (Full Range) [Months]	NA	NA	NA

12. Primary Outcome

Title	Percentage of Participants With Objective Response Rate for Part B, Part C, and Part D
Description	Objective response rate (ORR) is proportion of participants with CR or partial response (PR) as per IWG criteria. CR is disappearance of all evidence of disease. Nodal masses; FDG-avid/PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. Spleen; not palpable, nodules disappeared. Bone marrow; infiltrate cleared on repeat biopsy; if unknown by morphology, IHC was negative. PR is regression of measurable disease and no new sites. Nodal masses: >= 50% decrease in sum of the product diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. Spleen and liver: >= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone marrow: irrelevant if positive prior to therapy.
Time Frame	Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment.

Arm/Group Title	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	3	3	0	3	16	13
Number (95% Confidence Interval) [Percentage of participants]	66.7 2223.3%	33.3 832.5%	66.7 2223.3%	43.8 730%	23.1 770%

13. Primary Outcome

Title	Duration of Objective Response for Part B, Part C, and Part D
Description	Duration of objective response (DOR) is the first documentation of objective response to the first documented progressive disease (PD) or relapse according to IWG criteria. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) > 1.5 cm in any axis, >= 50% increase in SPD of more than one node, or >= 50% increase in longest diameter of a previously identified node > 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: > 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate DOR.
Time Frame	Cycle 1 Day 1, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment. The DOR were calculated for participants with objective response.

Arm/Group Title	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	2	1	0	2	7	3
Median (Full Range) [Months]	NA	27.5	3.7	NA	3.7

14. Primary Outcome

Title	Percentage of Participants With Disease Control Rate for Part B, Part C, and Part D
Description	Disease control includes CR, PR, or stable disease (SD) for at least 8 weeks according to IWG criteria. The CR is disappearance of all evidence of disease. Nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. Spleen; not palpable, nodules disappeared. Bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. PR is regression of measurable disease and no new sites. Nodal masses: >= 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) Variably FDG-avid or PET negative; regression on CT. Spleen and liver: >= 50% decrease in SPD of nodules; no increase in size of liver or spleen. For bone marrow: irrelevant if positive prior to therapy. SD is failure to attain CR/PR or PD.
Time Frame	Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment.

Arm/Group Title	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	3	3	0	3	11	6
Number (95% Confidence Interval) [Percentage of participants]	100 3333.3%	100 2500%	100 3333.3%	68.8 1146.7%	46.2 1540%

15. Primary Outcome

Title	Duration of Disease Control for Part B, Part C, and Part D
Description	Duration of disease control is defined as the time period from start of MEDI-551 administration to the event of PD/relapse. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) > 1.5 cm in any axis, >= 50% increase in SPD of more than one node, or >= 50% increase in longest diameter of a previously identified node > 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: > 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate duration of disease control.
Time Frame	Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment. Duration of disease control is calculated for the participants with objective response or stable disease response.

Arm/Group Title	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	3	3	0	3	11	6
Median (Full Range) [Months]	NA	29.8	5.5	14.6	3.8

16. Primary Outcome

Title	Time to Response for Part B, Part C, and Part D
Description	Time to response (TTR) is measured from the start of MEDI-551 administration to the first documentation of response (CR or PR) and assessed in participants who have achieved objective response. Kaplan-Meier method was used to evaluate TTR.
Time Frame	Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment. TTR were calculated for the participants with objective response.

Arm/Group Title	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	2	1	0	2	7	3
Median (Full Range) [Months]	6.5	12.0	1.8	2.0	1.8

17. Primary Outcome

Title	Progression Free Survival for Part B, Part C, and Part D
Description	Progression-free survival (PFS) is measured from the start of MEDI-551 treatment until the first documentation of disease progression, relapse or death, whichever occurs first. The PFS was censored on the date of last disease assessment for participants who have no documented PD/relapse or death prior to data cutoff, dropout, or the initiation of alternative anticancer therapy. Kaplan-Meier method was used to evaluate PFS.
Time Frame	Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment.

Arm/Group Title	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	3	3	0	3	16	13
Median (Full Range) [Months]	NA	29.8	5.5	3.5	2.0

18. Primary Outcome

Title	Overall Survival for Part B, Part C, and Part D
Description	Overall survival (OS) is measured from the start of MEDI-551 treatment until death. For participants who are alive at the end of study or lost to follow-up, OS will be censored on the last date when participants were known to be alive. Kaplan-Meier method was used to evaluate OS.
Time Frame	Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment.

Arm/Group Title	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	3	3	0	3	16	13
Median (Full Range) [Months]	NA	NA	25.0	33.4	17.9

19. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Part D
Description	An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Time Frame	Day 1 through 90-Day Post Last Dose (Approximately 9 years)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any treatment of MEDI-551.

Arm/Group Title	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	14
TEAEs	14 466.7%
TESAEs	5 166.7%

20. Secondary Outcome

Title	Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part D
Description	Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urine.
Time Frame	Day 1 through 90-Day Post Last Dose (Approximately 9 years)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any treatment of MEDI-551.

Arm/Group Title	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	14
Anemia	2 66.7%
Febrile neutropenia	1 33.3%
Lymphocyte count decreased	3 100%
Neutropenia	1 33.3%
Neutrophil count decreased	4 133.3%
Platelet count decreased	1 33.3%
Polycythemia	1 33.3%
Thrombocytopenia	2 66.7%
White blood cell count decreased	3 100%
Blood ALP increased	1 33.3%
Blood bilirubin increased	1 33.3%
Blood LDH increased	1 33.3%
Blood potassium decreased	1 33.3%
Hypercalcemia	1 33.3%
Hyperglycemia	2 66.7%
Hyperuricemia	2 66.7%
Hypocalcemia	1 33.3%
Hypokalemia	2 66.7%
Pollakiuria	1 33.3%
Urinary incontinence	1 33.3%

21. Secondary Outcome

Title	Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part D
Description	Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital signs parameters (temperature, blood pressure, pulse rate, respiratory rate, and pulse oximetry).
Time Frame	Day 1 through 90-Day Post Last Dose (Approximately 9 years)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any treatment of MEDI-551.

Arm/Group Title	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	14
Chills	2 66.7%
Dyspnea	1 33.3%
Hypertension	1 33.3%
Hypotension	1 33.3%
Palpitations	1 33.3%
Pyrexia	2 66.7%
Tachycardia	1 33.3%

22. Secondary Outcome

Title	Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part D
Description	Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs are defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, axis, and QT intervals from the primary lead of the digital 12-lead ECG.
Time Frame	Day 1 through 90-Day Post Last Dose (Approximately 9 years)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any treatment of MEDI-551.

Arm/Group Title	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	14
Count of Participants [Participants]	1 33.3%

23. Secondary Outcome

Title	Percentage of Participants With Complete Response for Part A
Description	The CR is defined as disappearance of all evidence of disease according to IWG criteria. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative .Variably FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative.
Time Frame	Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
Measure Participants	3	4	3	5	3	72
Number (95% Confidence Interval) [Percentage of Participants]	33.3 1110%	0 0%	0 0%	20.0 333.3%	0 0%	12.5 16.4%

24. Secondary Outcome

Title	Percentage of Participants With Partial Response for Part A
Description	The PR is defined as regression of measurable disease and no new sites according to IWG criteria. Nodal masses: >= 50% decrease in sum of the product diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. Spleen and liver: >= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone marrow: irrelevant if positive prior to therapy.
Time Frame	Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
Measure Participants	3	4	3	5	3	72
Number [Percentage of Participants]	33.3 1110%	0 0%	0 0%	0 0%	33.3 1110%	15.3 20.1%

25. Secondary Outcome

Title	Duration of Complete Response for Part A
Description	Duration of CR is from the first documentation of a CR to the time of progressive disease/relapse according to IWG criteria. The CR is disappearance of all evidence of disease. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. Variably FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. Kaplan-Meier method was used to evaluate duration of CR.
Time Frame	Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment. Duration of CR is calculated for participants with CR.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
Measure Participants	1	0	0	1	0	9
Median (Full Range) [Months]	7.1	14.9	14.3

26. Secondary Outcome

Title	Percentage of Participants With Objective Response Rate for Part A
Description	The ORR is defined as proportion of participants with CR or PR according to IWG criteria. CR is disappearance of all evidence of disease. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if unknown by morphology, IHC was negative. PR is regression of measurable disease and no new sites. For nodal masses: >= 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. For spleen and liver: >= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. For bone marrow: irrelevant if positive prior to therapy.
Time Frame	Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
Measure Participants	3	4	3	5	3	72
Number (95% Confidence Interval) [Percentage of participants]	66.7 2223.3%	0 0%	0 0%	20.0 333.3%	33.3 1110%	27.8 36.6%

27. Secondary Outcome

Title	Duration of Objective Response for Part A
Description	The DOR is the first documentation of objective response to the first documented PD or relapse according to IWG criteria. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) > 1.5 cm in any axis, >= 50% increase in SPD of more than one node, or >= 50% increase in longest diameter of a previously identified node > 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: > 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate DOR.
Time Frame	Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment. The DOR were calculated for participants with objective response.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
Measure Participants	2	0	0	1	1	20
Median (Full Range) [Months]	8.8	15.0	3.0	19.8

28. Secondary Outcome

Title	Percentage of Participants With Disease Control Rate for Part A
Description	Disease control includes CR, PR, or SD for at least 8 weeks according to IWG criteria. The CR is disappearance of all evidence of disease. For nodal masses; FDG -avid or PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. PR is regression of measurable disease and no new sites. For nodal masses: >= 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) Variably FDG-avid or PET negative; regression on CT. For spleen and liver: >= 50% decrease in SPD of nodules; no increase in size of liver or spleen. For bone marrow: irrelevant if positive prior to therapy. SD is failure to attain CR/PR or PD.
Time Frame	Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
Measure Participants	3	4	3	5	3	72
Number (95% Confidence Interval) [Percentage of participants]	66.7 2223.3%	50.0 1250%	66.7 2223.3%	80.0 1333.3%	66.7 2223.3%	73.6 96.8%

29. Secondary Outcome

Title	Duration of Disease Control for Part A
Description	Duration of disease control is defined as the time period from start of MEDI-551 administration to the event of PD/relapse according to IWG criteria. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) > 1.5 cm in any axis, >= 50% increase in SPD of more than one node, or >= 50% increase in longest diameter of a previously identified node > 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: > 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate duration of disease control.
Time Frame	Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment. Duration of disease control is calculated for the participants with objective response or stable disease response.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
Measure Participants	2	2	2	4	2	53
Median (Full Range) [Months]	12.6	NA	NA	10.9	6.6	18.0

30. Secondary Outcome

Title	Time to Response for Part A
Description	The TTR is measured from the start of MEDI-551 administration to the first documentation of response (CR or PR) and assessed in participants who have achieved objective response. Kaplan-Meier method was used to evaluate TTR.
Time Frame	Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment. TTR were calculated for the participants with objective response.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
Measure Participants	2	0	0	1	1	20
Median (Full Range) [Months]	3.7	1.9	3.6	3.2

31. Secondary Outcome

Title	Progression Free Survival for Part A
Description	The PFS is measured from the start of MEDI-551 treatment until the first documentation of disease progression, relapse or death, whichever occurs first. Kaplan-Meier method was used to evaluate PFS. The PFS was censored on the date of last disease assessment for participants who have no documented PD/relapse or death prior to data cutoff, dropout, or the initiation of alternative anticancer therapy.
Time Frame	Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
Measure Participants	3	4	3	5	3	72
Median (Full Range) [Months]	12.6	5.9	3.5	4.9	6.6	11.3

32. Secondary Outcome

Title	Overall Survival for Part A
Description	The OS is measured from the start of MEDI-551 treatment until death. For participants who are alive at the end of study or lost to follow-up, OS will be censored on the last date when participants were known to be alive. Kaplan-Meier method was used to evaluate OS.
Time Frame	Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
Measure Participants	3	4	3	5	3	72
Median (Full Range) [Months]	NA	44.6	9.9	NA	8.1	45.3

33. Secondary Outcome

Title	Trough Serum Concentration of MEDI-551 by Treatment Cycle
Description	Trough serum concentration (Ctrough) is defined as lowest concentration reached by a drug before the next dose is administered. The Ctrough concentration of MEDI-551 by treatment cycle is reported.
Time Frame	For Part A: C1D1 of each cycles; For Part B: C1D1 of each cycle + C1D8, C1D15, and C1D22; For Part C: C1D2, C1D8, then Day 1 of each cycle until Cycle 10;For Part D: C1D1, C1D8, then Day 1 of each cycle until Cycle 10

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included all participants who received at least one dose of MEDI-551 and had at least one measurable serum concentration of MEDI-551. The "Number of Participants Analyzed" denotes the number of participants evaluated for specific day.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg	Part A-MEDI-551 12 mg/kg (Expansion)	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	3	4	3	6	3	6	67	3	3	1	3	17	14
Cycle 1 (C1) Day 1 (D1)	NA (NA)	0.333 (0.665)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	2.97 (24.1)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)
C1D2	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)
C1D8	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	46.5 (20.9)	102 (25.0)	125 (NA)	58.0 (14.3)	115 (38.0)	109 (58.5)
C1D15	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	81.8 (38.3)	197 (51.2)	329 (NA)	NA (NA)	NA (NA)	NA (NA)
C1D22	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	116 (47.4)	281 (29.5)	NA (NA)	NA (NA)	NA (NA)
C2D1	15.6 (0.823)	25.9 (10.9)	12.9 (4.55)	59.4 (11.0)	89.8 (64.9)	166 (54.0)	124 (64.8)	122 (37.2)	326 (68.0)	52.4 (17.7)	106 (28.8)	114 (40.1)
C3D1	19.3 (3.33)	26.9 (12.2)	6.78 (2.01)	43.0 (8.40)	97.0 (94.5)	149 (46.2)	113 (70.3)	57.6 (43.1)	187 (80.6)	44.7 (14.2)	92.1 (30.7)	93.9 (35.6)
C4D1	20.9 (6.69)	36.5 (0.550)	5.59 (0.146)	37.9 (13.8)	33.4 (NA)	146 (55.5)	113 (57.1)	36.0 (31.6)	134 (67.7)	48.2 (20.8)	113 (70.0)	102 (61.5)
C5D1	26.6 (7.17)	46.8 (8.03)	56.9 (19.6)	31.8 (NA)	136 (19.3)	117 (60.9)	35.7 (32.0)	121 (78.1)	51.6 (2.64)	102 (26.3)	147 (105)
C6D1	29.1 (6.17)	29.1 (17.3)	11.7 (NA)	32.0 (NA)	33.7 (NA)	138 (27.2)	123 (67.9)	37.3 (33.5)	106 (54.6)	45.9 (NA)	100 (22.9)	150 (116)
C7D1	31.4 (7.08)	25.1 (27.8)	9.93 (NA)	38.2 (NA)	27.9 (NA)	144 (42.4)	109 (64.2)	28.1 (21.2)	95.1 (54.4)	45.3 (NA)	108 (20.2)	248 (NA)
C8D1	27.1 (14.9)	28.0 (1.86)	8.80 (NA)	33.3 (NA)	109 (NA)	114 (63.8)	30.8 (30.4)	86.8 (54.4)	147 (82.2)	177 (NA)
C9D1	21.6 (NA)	31.6 (1.23)	10.7 (NA)	33.6 (NA)	124 (23.2)	121 (77.5)	27.3 (27.1)	94.8 (69.4)	95.0 (7.59)	192 (25.9)
C10D1	17.6 (NA)	25.1 (NA)	10.6 (NA)	32.9 (NA)	98.3 (5.05)	139 (80.4)	33.4 (34.8)	84.2 (57.4)	113 (27.6)	215 (NA)

34. Secondary Outcome

Title	Peak Serum Concentration of MEDI-551 by Treatment Cycle
Description	Peak serum concentration is concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and before the administration of a second dose.
Time Frame	For Part A: C1D1 of each cycles; For Part B: C1D1 of each cycle + C1D8, C1D15, and C1D22; For Part C: C1D2, C1D8, then Day 1 of each cycle until Cycle 10;For Part D: C1D1, C1D8, then Day 1 of each cycle until Cycle 10

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included all participants who received at least one dose of MEDI-551 and had at least one measurable serum concentration of MEDI-551. The "Number of Participants Analyzed" denotes the number of participants evaluated for specific day.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg	Part A-MEDI-551 12 mg/kg (Expansion)	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	3	4	3	6	3	6	67	3	3	1	3	17	14
Cycle 1 (C1) Day 1 (D1)	12.3 (1.20)	22.8 (1.24)	46.0 (22.2)	100 (11.0)	166 (59.5)	280 (99.1)	240 (90.0)	122 (24.2)	335 (79.1)	199 (NA)	NA (NA)	NA (NA)	260 (87.3)
C1D2	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	160 (23.5)	214 (79.9)	NA (NA)
C1D8	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	162 (17.3)	393 (80.8)	470 (NA)	246 (76.1)	115 (38.0)	303 (97.4)
C1D15	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	182 (31.1)	517 (135)	619 (NA)	NA (NA)	NA (NA)	NA (NA)
C1D22	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	208 (46.7)	533 (223)	NA (NA)	NA (NA)	NA (NA)
C2D1	27.5 (0.752)	43.9 (13.2)	48.8 (21.7)	149 (29.7)	238 (106)	467 (114)	350 (130)	186 (116)	749 (133)	205 (33.5)	304 (108)	333 (72.7)
C3D1	26.3 (2.20)	46.4 (16.6)	58.7 (0.783)	145 (31.2)	260 (89.6)	374 (116)	326 (110)	155 (38.2)	374 (125)	192 (78.1)	311 (74.0)	277 (95.7)
C4D1	30.3 (5.46)	48.3 (12.7)	63.7 (35.1)	161 (85.6)	201 (NA)	359 (115)	342 (119)	156 (81.7)	384 (169)	212 (84.1)	261 (99.4)	295 (116)
C5D1	39.4 (6.85)	70.8 (5.43)	151 (58.1)	203 (NA)	372 (113)	347 (98.1)	153 (71.6)	363 (261)	250 (82.3)	290 (66.0)	338 (245)
C6D1	40.4 (3.87)	34.4 (4.21)	43.2 (NA)	123 (NA)	198 (NA)	345 (101)	337 (82.1)	130 (45.7)	349 (140)	209 (NA)	332 (102)	303 (237)
C7D1	41.3 (4.72)	39.5 (30.8)	41.0 (NA)	123 (NA)	182 (NA)	383 (54.6)	355 (95.7)	174 (60.4)	333 (133)	235 (NA)	392 (93.0)	502 (NA)
C8D1	29.9 (12.3)	58.2 (16.9)	32.2 (NA)	130 (NA)	409 (NA)	367 (102)	164 (52.0)	342 (173)	317 (150)	511 (NA)
C9D1	32.2 (NA)	46.8 (5.58)	37.8 (NA)	127 (NA)	391 (79.6)	394 (125)	159 (64.7)	299 (69.8)	363 (90.3)	593 (200)
C10D1	43.3 (NA)	33.5 (NA)	42.3 (NA)	133 (NA)	307 (49.8)	394 (157)	166 (64.1)	316 (189)	349 (70.4)	484 (NA)

35. Secondary Outcome

Title	Area Under the Concentration Curve at Steady State (AUCss) of MEDI-551
Description	Area under the concentration-time curve at steady state (Css, AUC) of MEDI-551 is reported.
Time Frame	Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included all participants who received at least one dose of MEDI-551 and had at least one measurable serum concentration of MEDI-551.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg	Part A-MEDI-551 12 mg/kg (Expansion)	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	3	4	3	6	3	6	67	3	3	1	3	17	14
Mean (Standard Deviation) [μg⋅day/mL]	212 (28.1)	287 (110)	479 (57.7)	1660 (778)	2880 (2190)	5720 (1620)	4850 (1720)	1730 (1030)	4920 (1440)	NA (NA)	2240 (338)	4260 (1340)	4250 (2000)

36. Secondary Outcome

Title	Apparent Clearance of MEDI-551
Description	Apparent clearance of MEDI-551 is reported.
Time Frame	Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24

Outcome Measure Data

Analysis Population Description

Population pharmacokinetic model included all participants who received at least one dose of MEDI-551 and provided at least one measurable serum concentration of MEDI-551.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg	Part A-MEDI-551 12 mg/kg (Expansion)	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	3	4	3	6	3	6	67	3	3	1	3	17	14
Mean (Standard Deviation) [mL/day]	206 (101)	302 (173)	373 (70.9)	210 (28.9)	268 (126)	198 (44.3)	235 (110)	303 (108)	243 (81.6)	279 (NA)	288 (43.0)	235 (87.5)	237 (72.5)

37. Secondary Outcome

Title	Volume of Distribution of MEDI-551
Description	Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Central volume of distribution (Vd1) is defined as hypothetical volume into which a drug initially distributes upon administration and peripheral volume of distribution (Vd2) is defined as the sum of all tissue spaces outside the central compartment.
Time Frame	Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included all participants who received at least one dose of MEDI-551 and had at least one measurable serum concentration of MEDI-551.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg	Part A-MEDI-551 12 mg/kg (Expansion)	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	3	4	3	6	3	6	67	3	3	1	3	17	14
Vd1	3970 (851)	3920 (491)	4350 (948)	4070 (464)	4210 (510)	4230 (234)	4450 (889)	3560 (286)	4490 (947)	5690 (NA)	4520 (126)	4350 (851)	4510 (647)
Vd2	2670 (351)	2010 (1080)	1980 (888)	2290 (767)	2620 (1240)	2920 (1070)	3430 (2250)	3290 (1440)	2640 (1840)	3670 (NA)	4590 (847)	2640 (1200)	3200 (1440)

38. Secondary Outcome

Title	Terminal Half-life (t1/2) of MEDI-551
Description	Terminal half-life is the time required for the plasma concentration of MEDI-551 to fall by 50% during the terminal phase.
Time Frame	Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included all participants who received at least one dose of MEDI-551 and had at least one measurable serum concentration of MEDI-551.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg	Part A-MEDI-551 12 mg/kg (Expansion)	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	3	4	3	6	3	6	67	3	3	1	3	17	14
Mean (Standard Deviation) [Days]	26.0 (6.88)	17.3 (7.65)	13.3 (6.41)	22.1 (3.26)	21.7 (8.65)	27.9 (9.08)	28.9 (15.0)	19.9 (9.34)	23.8 (10.9)	25.1 (NA)	25.3 (4.40)	23.6 (9.38)	25.6 (7.96)

39. Secondary Outcome

Title	Number of Participants With Positive Anti-drug Antibodies (ADA) Titer to MEDI-551
Description	Number of participants with positive Anti-drug antibodies (ADA) titer to MEDI-551 is reported.
Time Frame	Part A:C1D1; Part B: C1D1; Part C: C1D1; Part D: C1D1; End of treatment (EOT); 90 Days post last dose (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any treatment of MEDI-551. Participants only with positive ADA is reported.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	3	4	3	6	3	76	3	3	3	17	14
C1D1	0 0%	1 25%	0 0%	0 0%	0 0%	2 2.6%	0 0%	0 0%	0 0%	0 0%	2 11.8%
EOT	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
90 Day Post Dose	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

40. Secondary Outcome

Title	B-cell Concentration in Serum
Description	B-cell Concentration in serum is reported.
Time Frame	Part A:C1D1 of each cycles; Part B: C1D1 of each cycle + C1D8, C1D15, and C1D22; Part C: C1D2, C1D8, then Day 1 of each cycle until Cycle 10; Part D: C1D1, C1D8, Day 1 of each cycle until Cycle 10; EOT;90 Days post last dose (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any treatment of MEDI-551. It was pre-specified that B-cell analysis was not required, due to limited data availability.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg	Part B-MEDI-551 6 mg/kg	Part B-MEDI-551 12 mg/kg	Part B-MEDI-551 24 mg/kg	Part C-MEDI-551 8 mg/kg + Rituximab	Part C-MEDI-551 12 mg/kg + Rituximab	Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
Measure Participants	0	0	0	0	0	0	0	0	0	0	0	0

41. Secondary Outcome

Title	Immunoglobulin (Ig) Concentration in Serum
Description	Immunoglobin (Ig) concentration in serum is reported.
Time Frame	Part A:C1D1 of each cycles; EOT;90 Days post last dose (approximately 9 years)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received any treatment of MEDI-551.

Arm/Group Title	Part A-MEDI-551 0.5 mg/kg	Part A-MEDI-551 1 mg/kg	Part A-MEDI-551 2 mg/kg	Part A-MEDI-551 4 mg/kg	Part A-MEDI-551 8 mg/kg	Part A-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.	Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
Measure Participants	3	4	3	6	3	76
C1D1	120.00 (46.36)	110.00 (76.25)	81.00 (66.36)	61.67 (54.52)	93.33 (46.11)	93.01 (88.56)
C2D1	67.50 (7.78)	113.67 (92.81)	67.67 (58.05)	57.00 (47.05)	74.50 (47.38)	88.90 (92.05)
C3D1	62.50 (6.36)	106.00 (87.93)	31.00 (29.70)	57.25 (48.29)	76.50 (50.20)	67.90 (66.59)
C4D1	64.00 (9.90)	152.50 (13.44)	31.00 (33.94)	63.67 (56.52)	98.00 (NA)	66.84 (61.83)
C5D1	69.00 (11.31)	145.50 (38.89)	50.00 (NA)	58.67 (45.17)	77.00 (NA)	69.24 (70.45)
C6D1	63.50 (13.44)	156.00 (48.08)	41.00 (NA)	71.00 (NA)	62.86 (65.04)
C7D1	56.00 (1.41)	127.00 (NA)	47.00 (NA)	41.00 (NA)	61.00 (NA)	67.26 (69.36)
C8D1	47.00 (7.07)	147.00 (28.28)	45.00 (NA)	41.00 (NA)	73.76 (66.87)
C9D1	51.00 (NA)	137.50 (30.41)	46.00 (NA)	41.00 (NA)	62.35 (61.90)
C10D1	47.00 (NA)	155.00 (NA)	46.00 (NA)	41.00 (NA)	73.17 (66.34)
EOT	43.50 (12.02)	96.00 (80.58)	7.00 (NA)	54.40 (46.55)	65.33 (19.76)	217.25 (1003.38)
90 Days Post Dose	49.00 (NA)	84.50 (60.10)	93.33 (42.06)	45.20 (38.72)

Adverse Events

Time Frame	Day 1 through 90-Day Post Last Dose (Approximately 9 years)
Arm/Group Title	Part A-MEDI-551 0.5 mg/kg		Part A-MEDI-551 1 mg/kg		Part A-MEDI-551 2 mg/kg		Part A-MEDI-551 4 mg/kg		Part A-MEDI-551 8 mg/kg		Part A-MEDI-551 12 mg/kg		Part B-MEDI-551 6 mg/kg		Part B-MEDI-551 12 mg/kg		Part B-MEDI-551 24 mg/kg		Part C-MEDI-551 8 mg/kg + Rituximab		Part C-MEDI-551 12 mg/kg + Rituximab		Part D-MEDI-551 12 mg/kg
Arm/Group Description	Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.		Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.		Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.		Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.		Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.		Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.		Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.		Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.		Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.		Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.		Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.		Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
All Cause Mortality
	Part A-MEDI-551 0.5 mg/kg		Part A-MEDI-551 1 mg/kg		Part A-MEDI-551 2 mg/kg		Part A-MEDI-551 4 mg/kg		Part A-MEDI-551 8 mg/kg		Part A-MEDI-551 12 mg/kg		Part B-MEDI-551 6 mg/kg		Part B-MEDI-551 12 mg/kg		Part B-MEDI-551 24 mg/kg		Part C-MEDI-551 8 mg/kg + Rituximab		Part C-MEDI-551 12 mg/kg + Rituximab		Part D-MEDI-551 12 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		2/4 (50%)		2/3 (66.7%)		1/6 (16.7%)		2/3 (66.7%)		30/76 (39.5%)		1/3 (33.3%)		0/3 (0%)		1/1 (100%)		2/3 (66.7%)		9/17 (52.9%)		8/14 (57.1%)
Serious Adverse Events
	Part A-MEDI-551 0.5 mg/kg		Part A-MEDI-551 1 mg/kg		Part A-MEDI-551 2 mg/kg		Part A-MEDI-551 4 mg/kg		Part A-MEDI-551 8 mg/kg		Part A-MEDI-551 12 mg/kg		Part B-MEDI-551 6 mg/kg		Part B-MEDI-551 12 mg/kg		Part B-MEDI-551 24 mg/kg		Part C-MEDI-551 8 mg/kg + Rituximab		Part C-MEDI-551 12 mg/kg + Rituximab		Part D-MEDI-551 12 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		1/4 (25%)		2/3 (66.7%)		1/6 (16.7%)		1/3 (33.3%)		23/76 (30.3%)		1/3 (33.3%)		2/3 (66.7%)		1/1 (100%)		1/3 (33.3%)		9/17 (52.9%)		5/14 (35.7%)
Blood and lymphatic system disorders
Anaemia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Febrile neutropenia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Neutropenia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Cardiac disorders
Sinus bradycardia	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Abdominal pain upper	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Faecaloma	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Nausea	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Pancreatitis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Vomiting	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
General disorders
General physical health deterioration	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Non-cardiac chest pain	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Pyrexia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	4	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Hepatobiliary disorders
Acute hepatic failure	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Cholecystitis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Infections and infestations
Abscess limb	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Bacteraemia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Bronchitis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	2	1/14 (7.1%)	1
Gastroenteritis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Lung infection	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Pneumonia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	2/76 (2.6%)	3	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	2/14 (14.3%)	2
Sepsis syndrome	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Septic shock	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Sinusitis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Staphylococcal sepsis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Varicella	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Injury, poisoning and procedural complications
Fall	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Infusion related reaction	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	6	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Procedural haemorrhage	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Procedural pain	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Spinal compression fracture	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Subarachnoid haemorrhage	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	1/14 (7.1%)	1
Hypercalcaemia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Intervertebral disc protrusion	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Lumbar spinal stenosis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Musculoskeletal chest pain	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	1	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Osteolysis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Adenocarcinoma of colon	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
B-cell lymphoma	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Diffuse large b-cell lymphoma	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	2	0/14 (0%)	0
Malignant melanoma	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/17 (0%)	0	0/14 (0%)	0
Non-hodgkin's lymphoma	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Polycythaemia vera	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Squamous cell carcinoma	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Nervous system disorders
Cauda equina syndrome	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Syncope	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Toxic encephalopathy	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Psychiatric disorders
Confusional state	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Mental status changes	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Renal and urinary disorders
Acute kidney injury	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Dysuria	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchiectasis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Dyspnoea	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Pneumothorax	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Pulmonary embolism	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Pulmonary haemorrhage	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Respiratory failure	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Skin and subcutaneous tissue disorders
Pemphigoid	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Vascular disorders
Deep vein thrombosis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	1	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Haematoma	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Hypotension	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Shock haemorrhagic	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Other (Not Including Serious) Adverse Events
	Part A-MEDI-551 0.5 mg/kg		Part A-MEDI-551 1 mg/kg		Part A-MEDI-551 2 mg/kg		Part A-MEDI-551 4 mg/kg		Part A-MEDI-551 8 mg/kg		Part A-MEDI-551 12 mg/kg		Part B-MEDI-551 6 mg/kg		Part B-MEDI-551 12 mg/kg		Part B-MEDI-551 24 mg/kg		Part C-MEDI-551 8 mg/kg + Rituximab		Part C-MEDI-551 12 mg/kg + Rituximab		Part D-MEDI-551 12 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		4/4 (100%)		3/3 (100%)		6/6 (100%)		3/3 (100%)		75/76 (98.7%)		3/3 (100%)		3/3 (100%)		1/1 (100%)		3/3 (100%)		17/17 (100%)		14/14 (100%)
Blood and lymphatic system disorders
Anaemia	0/3 (0%)	0	2/4 (50%)	2	0/3 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	6/76 (7.9%)	8	0/3 (0%)	0	1/3 (33.3%)	1	1/1 (100%)	2	0/3 (0%)	0	4/17 (23.5%)	18	2/14 (14.3%)	3
Febrile neutropenia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Hypergammaglobulinaemia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Increased tendency to bruise	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Leukocytosis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Leukopenia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	1/3 (33.3%)	5	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Lymph node pain	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	2	0/14 (0%)	0
Lymphopenia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Neutropenia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	1/3 (33.3%)	1	13/76 (17.1%)	19	1/3 (33.3%)	1	1/3 (33.3%)	13	0/1 (0%)	0	1/3 (33.3%)	1	2/17 (11.8%)	7	1/14 (7.1%)	2
Polycythaemia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Splenomegaly	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Thrombocytopenia	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	3/6 (50%)	7	0/3 (0%)	0	6/76 (7.9%)	7	0/3 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	19	2/14 (14.3%)	4
Cardiac disorders
Angina pectoris	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Atrial fibrillation	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	3	0/3 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Atrial flutter	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Atrial tachycardia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	3	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Bradycardia	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Cardiac failure chronic	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Mitral valve incompetence	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/17 (0%)	0	0/14 (0%)	0
Palpitations	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	2	1/14 (7.1%)	1
Supraventricular tachycardia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Tachycardia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	6/76 (7.9%)	7	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	2	1/14 (7.1%)	1
Ear and labyrinth disorders
Cerumen impaction	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Deafness	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Ear pain	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	3	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	2	0/14 (0%)	0
Ear swelling	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Excessive cerumen production	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Hypoacusis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Otorrhoea	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/17 (0%)	0	0/14 (0%)	0
Vertigo	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	2
Endocrine disorders
Hypothyroidism	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Eye disorders
Cataract	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Dry eye	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Exophthalmos	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Eye pruritus	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Glaucoma	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Ocular hyperaemia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Vision blurred	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	1	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	3	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Abdominal distension	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	3	0/3 (0%)	0	1/3 (33.3%)	4	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Abdominal pain	0/3 (0%)	0	2/4 (50%)	3	0/3 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	6/76 (7.9%)	7	0/3 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	3	1/14 (7.1%)	1
Abdominal pain lower	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	2	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Abdominal pain upper	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	4/76 (5.3%)	4	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Anal incontinence	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Constipation	0/3 (0%)	0	1/4 (25%)	5	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	10/76 (13.2%)	12	1/3 (33.3%)	1	1/3 (33.3%)	3	0/1 (0%)	0	1/3 (33.3%)	1	6/17 (35.3%)	7	2/14 (14.3%)	2
Dental caries	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Diarrhoea	3/3 (100%)	10	2/4 (50%)	4	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	18/76 (23.7%)	21	1/3 (33.3%)	1	2/3 (66.7%)	3	1/1 (100%)	2	1/3 (33.3%)	1	5/17 (29.4%)	15	3/14 (21.4%)	4
Dry mouth	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	3	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	1	0/3 (0%)	0	1/17 (5.9%)	2	1/14 (7.1%)	1
Dyspepsia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	3	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Dysphagia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	2	0/14 (0%)	0
Gastrooesophageal reflux disease	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	1/76 (1.3%)	1	1/3 (33.3%)	1	2/3 (66.7%)	3	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	2	1/14 (7.1%)	3
Gingival pain	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Impaired gastric emptying	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Inguinal hernia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Intestinal ischaemia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Lip dry	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Nausea	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	1/3 (33.3%)	1	13/76 (17.1%)	16	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	1/3 (33.3%)	2	5/17 (29.4%)	9	3/14 (21.4%)	3
Oesophageal stenosis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Oral pain	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Salivary hypersecretion	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Stomatitis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	2	0/14 (0%)	0
Tongue coated	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Toothache	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Upper gastrointestinal haemorrhage	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Vomiting	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	7/76 (9.2%)	8	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	1/3 (33.3%)	1	4/17 (23.5%)	6	0/14 (0%)	0
General disorders
Asthenia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	5/76 (6.6%)	6	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	4	0/14 (0%)	0
Breakthrough pain	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Chills	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	5/76 (6.6%)	6	0/3 (0%)	0	1/3 (33.3%)	4	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	2/14 (14.3%)	3
Cyst	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Early satiety	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/17 (0%)	0	0/14 (0%)	0
Fatigue	1/3 (33.3%)	1	1/4 (25%)	5	1/3 (33.3%)	1	2/6 (33.3%)	2	3/3 (100%)	3	28/76 (36.8%)	33	2/3 (66.7%)	2	3/3 (100%)	6	0/1 (0%)	0	1/3 (33.3%)	2	9/17 (52.9%)	20	5/14 (35.7%)	6
Gait disturbance	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	3/17 (17.6%)	3	1/14 (7.1%)	1
Gravitational oedema	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Ill-defined disorder	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Influenza like illness	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Infusion site pain	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Localised oedema	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Malaise	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	3	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Mass	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/17 (0%)	0	0/14 (0%)	0
Medical device site bruise	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Medical device site pain	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Mucosal inflammation	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	2	0/14 (0%)	0
Necrosis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	2	0/14 (0%)	0
Non-cardiac chest pain	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	3	0/1 (0%)	0	1/3 (33.3%)	1	0/17 (0%)	0	0/14 (0%)	0
Oedema	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Oedema peripheral	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	8/76 (10.5%)	9	0/3 (0%)	0	2/3 (66.7%)	5	1/1 (100%)	2	0/3 (0%)	0	5/17 (29.4%)	9	2/14 (14.3%)	2
Pain	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	4/76 (5.3%)	4	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Performance status decreased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Peripheral swelling	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	5/76 (6.6%)	9	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	2	0/14 (0%)	0
Pyrexia	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	2/6 (33.3%)	2	0/3 (0%)	0	13/76 (17.1%)	18	1/3 (33.3%)	1	1/3 (33.3%)	4	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	3	2/14 (14.3%)	2
Systemic inflammatory response syndrome	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Hepatobiliary disorders
Hyperbilirubinaemia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	2	0/14 (0%)	0
Immune system disorders
Hypogammaglobulinaemia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	2	0/3 (0%)	0	0/76 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Immune system disorder	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Seasonal allergy	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Infections and infestations
Abscess limb	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Bacterial vaginosis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Bronchitis	0/3 (0%)	0	1/4 (25%)	1	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	4/76 (5.3%)	6	2/3 (66.7%)	2	2/3 (66.7%)	3	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	1/14 (7.1%)	3
Candida infection	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Cellulitis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	3	0/14 (0%)	0
Chronic sinusitis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Conjunctivitis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	3	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Diverticulitis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	3	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Ear infection	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	1/17 (5.9%)	7	1/14 (7.1%)	1
Furuncle	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Gastroenteritis viral	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Herpes zoster	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	4	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Influenza	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Laryngitis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	3	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Nasopharyngitis	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	4/76 (5.3%)	5	0/3 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Oral herpes	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	2/6 (33.3%)	3	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	4	0/14 (0%)	0
Pharyngitis	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Pneumonia	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	2/3 (66.7%)	3	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	2	1/14 (7.1%)	2
Pyelonephritis acute	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Rash pustular	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	1/3 (33.3%)	2	0/3 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/17 (0%)	0	0/14 (0%)	0
Respiratory tract infection	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Rhinitis	0/3 (0%)	0	1/4 (25%)	1	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Sinusitis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	4/76 (5.3%)	4	1/3 (33.3%)	6	1/3 (33.3%)	2	0/1 (0%)	0	0/3 (0%)	0	4/17 (23.5%)	8	2/14 (14.3%)	2
Tonsillitis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Tooth infection	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Upper respiratory tract infection	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	9/76 (11.8%)	11	2/3 (66.7%)	6	1/3 (33.3%)	10	0/1 (0%)	0	0/3 (0%)	0	3/17 (17.6%)	4	2/14 (14.3%)	2
Urinary tract infection	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	2	0/6 (0%)	0	0/3 (0%)	0	8/76 (10.5%)	9	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	3	0/14 (0%)	0
Viral infection	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Injury, poisoning and procedural complications
Contusion	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	1/6 (16.7%)	2	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	1	0/3 (0%)	0	2/17 (11.8%)	3	0/14 (0%)	0
Fall	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	2	0/3 (0%)	0	1/17 (5.9%)	1	1/14 (7.1%)	1
Infusion related reaction	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	2/6 (33.3%)	2	0/3 (0%)	0	34/76 (44.7%)	108	1/3 (33.3%)	6	2/3 (66.7%)	8	1/1 (100%)	1	0/3 (0%)	0	1/17 (5.9%)	1	4/14 (28.6%)	12
Laceration	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	3	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Limb injury	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Post-traumatic pain	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Procedural complication	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Procedural pain	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	3	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Rib fracture	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	1	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Skin abrasion	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Vascular access complication	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Wrong drug administered	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Investigations
Activated partial thromboplastin time prolonged	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	2	0/14 (0%)	0
Alanine aminotransferase increased	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	3	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	2	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Aspartate aminotransferase increased	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	4/76 (5.3%)	4	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	3	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Blood albumin decreased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Blood alkaline phosphatase increased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	2	0/3 (0%)	0	2/17 (11.8%)	4	1/14 (7.1%)	1
Blood bilirubin increased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Blood chloride decreased	0/3 (0%)	0	1/4 (25%)	2	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Blood cholesterol increased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Blood creatinine increased	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	1/3 (33.3%)	1	1/1 (100%)	1	0/3 (0%)	0	2/17 (11.8%)	2	0/14 (0%)	0
Blood fibrinogen decreased	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Blood fibrinogen increased	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Blood immunoglobulin m decreased	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Blood iron decreased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Blood lactate dehydrogenase increased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	3	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	1	0/3 (0%)	0	1/17 (5.9%)	1	1/14 (7.1%)	1
Blood phosphorus decreased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Blood potassium decreased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	2
Blood triglycerides increased	1/3 (33.3%)	5	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Blood urea increased	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
C-reactive protein increased	0/3 (0%)	0	1/4 (25%)	1	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	1/3 (33.3%)	5	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Electrocardiogram qt prolonged	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	1/14 (7.1%)	1
Gamma-glutamyltransferase increased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	4	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Glucose urine present	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Haematocrit decreased	0/3 (0%)	0	1/4 (25%)	2	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Karnofsky scale worsened	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Low density lipoprotein increased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Lymphocyte count decreased	0/3 (0%)	0	1/4 (25%)	4	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	11	0/3 (0%)	0	2/17 (11.8%)	7	3/14 (21.4%)	3
Mean cell volume increased	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Neutrophil count abnormal	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Neutrophil count decreased	1/3 (33.3%)	2	1/4 (25%)	5	0/3 (0%)	0	1/6 (16.7%)	4	0/3 (0%)	0	5/76 (6.6%)	7	0/3 (0%)	0	1/3 (33.3%)	3	1/1 (100%)	1	0/3 (0%)	0	2/17 (11.8%)	2	4/14 (28.6%)	4
Occult blood positive	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Platelet count decreased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	3	0/3 (0%)	0	1/3 (33.3%)	1	1/1 (100%)	1	0/3 (0%)	0	1/17 (5.9%)	1	1/14 (7.1%)	1
Prostatic specific antigen increased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Protein total decreased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Red blood cell count decreased	0/3 (0%)	0	1/4 (25%)	2	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Serum ferritin decreased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Vitamin d decreased	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Weight decreased	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	3	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	1/14 (7.1%)	1
Weight increased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	5	0/14 (0%)	0
White blood cell count decreased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	1/3 (33.3%)	1	3/76 (3.9%)	4	0/3 (0%)	0	2/3 (66.7%)	4	1/1 (100%)	8	0/3 (0%)	0	2/17 (11.8%)	4	3/14 (21.4%)	4
Metabolism and nutrition disorders
Decreased appetite	0/3 (0%)	0	2/4 (50%)	2	1/3 (33.3%)	1	1/6 (16.7%)	1	0/3 (0%)	0	7/76 (9.2%)	7	0/3 (0%)	0	1/3 (33.3%)	1	1/1 (100%)	1	0/3 (0%)	0	2/17 (11.8%)	2	5/14 (35.7%)	6
Dehydration	0/3 (0%)	0	1/4 (25%)	2	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Hypercalcaemia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	3	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Hyperglycaemia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	1/76 (1.3%)	7	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	4	2/14 (14.3%)	2
Hyperkalaemia	0/3 (0%)	0	2/4 (50%)	6	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Hypernatraemia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	2	0/3 (0%)	0	2/17 (11.8%)	3	0/14 (0%)	0
Hypertriglyceridaemia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	4/76 (5.3%)	5	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Hyperuricaemia	1/3 (33.3%)	2	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	4	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	2	0/3 (0%)	0	1/17 (5.9%)	1	2/14 (14.3%)	2
Hypoalbuminaemia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	3	0/3 (0%)	0	2/17 (11.8%)	6	0/14 (0%)	0
Hypocalcaemia	0/3 (0%)	0	2/4 (50%)	2	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/1 (100%)	2	0/3 (0%)	0	2/17 (11.8%)	2	1/14 (7.1%)	1
Hypoglycaemia	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Hypokalaemia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	5	2/14 (14.3%)	2
Hypomagnesaemia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	5	0/14 (0%)	0
Hyponatraemia	0/3 (0%)	0	1/4 (25%)	6	0/3 (0%)	0	1/6 (16.7%)	2	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	6	0/14 (0%)	0
Hypophosphataemia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	3	0/14 (0%)	0
Vitamin d deficiency	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	6/76 (7.9%)	9	0/3 (0%)	0	2/3 (66.7%)	5	0/1 (0%)	0	1/3 (33.3%)	1	3/17 (17.6%)	6	0/14 (0%)	0
Arthritis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Back pain	1/3 (33.3%)	2	2/4 (50%)	2	0/3 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	2	11/76 (14.5%)	12	0/3 (0%)	0	2/3 (66.7%)	4	0/1 (0%)	0	2/3 (66.7%)	2	4/17 (23.5%)	5	2/14 (14.3%)	6
Bone pain	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	5	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	2	0/14 (0%)	0
Bursitis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Groin pain	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	2/76 (2.6%)	3	1/3 (33.3%)	1	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Inguinal mass	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Joint swelling	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Muscle spasms	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	9/76 (11.8%)	11	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	2/14 (14.3%)	3
Muscular weakness	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	1	0/3 (0%)	0	2/17 (11.8%)	2	0/14 (0%)	0
Musculoskeletal chest pain	0/3 (0%)	0	1/4 (25%)	1	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	1/3 (33.3%)	2	1/1 (100%)	1	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Musculoskeletal pain	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	3	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	5	1/14 (7.1%)	2
Musculoskeletal stiffness	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	2	0/14 (0%)	0
Myalgia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	4/76 (5.3%)	4	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	3	0/14 (0%)	0
Osteoarthritis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Osteonecrosis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Pain in extremity	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	6/76 (7.9%)	9	1/3 (33.3%)	1	1/3 (33.3%)	2	0/1 (0%)	0	0/3 (0%)	0	5/17 (29.4%)	6	0/14 (0%)	0
Pain in jaw	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Sarcopenia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Spondylitis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Benign neoplasm of thyroid gland	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Bowen's disease	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Haemangioma	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Melanocytic naevus	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Metastatic lymphoma	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Seborrhoeic keratosis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	2	0/14 (0%)	0
Skin papilloma	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Squamous cell carcinoma	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	2	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	2	0/14 (0%)	0
Squamous cell carcinoma of skin	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	1/3 (33.3%)	1	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Tumour pain	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Nervous system disorders
Amnesia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Anosmia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Cerebrovascular accident	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	1	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Dizziness	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	10/76 (13.2%)	12	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	1	0/3 (0%)	0	1/17 (5.9%)	2	3/14 (21.4%)	4
Dysgeusia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Headache	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	15/76 (19.7%)	20	0/3 (0%)	0	1/3 (33.3%)	7	0/1 (0%)	0	0/3 (0%)	0	3/17 (17.6%)	3	0/14 (0%)	0
Hypersomnia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Hypoaesthesia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	4/76 (5.3%)	4	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Memory impairment	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Neuropathy peripheral	2/3 (66.7%)	2	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	1/17 (5.9%)	1	0/14 (0%)	0
Paraesthesia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	4	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	2	0/14 (0%)	0
Peripheral sensory neuropathy	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Presyncope	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Sciatica	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	1/3 (33.3%)	2	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	3	0/14 (0%)	0
Seizure	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Sinus headache	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Somnolence	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Syncope	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	3	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Tremor	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Product Issues
Device dislocation	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Psychiatric disorders
Aggression	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Agitation	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	1/14 (7.1%)	1
Anxiety	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	8/76 (10.5%)	8	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	1/3 (33.3%)	1	2/17 (11.8%)	4	1/14 (7.1%)	1
Confusional state	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	2	2/14 (14.3%)	2
Depressed mood	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Depression	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	3	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	3/17 (17.6%)	3	1/14 (7.1%)	1
Hallucination	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Hallucinations, mixed	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Insomnia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	8/76 (10.5%)	8	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	5	4/14 (28.6%)	4
Mental status changes	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Sleep disorder	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Renal and urinary disorders
Bladder spasm	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Dysuria	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Haematuria	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	2	0/14 (0%)	0
Haemoglobinuria	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	3	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Hydronephrosis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	2	0/14 (0%)	0
Micturition urgency	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Pollakiuria	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Urinary incontinence	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	1/14 (7.1%)	1
Urinary retention	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Urine flow decreased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Reproductive system and breast disorders
Breast swelling	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Erectile dysfunction	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Haematospermia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Nipple disorder	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/3 (33.3%)	1	2/4 (50%)	3	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	26/76 (34.2%)	31	1/3 (33.3%)	1	3/3 (100%)	7	0/1 (0%)	0	0/3 (0%)	0	3/17 (17.6%)	3	2/14 (14.3%)	5
Dry throat	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Dyspnoea	0/3 (0%)	0	1/4 (25%)	1	1/3 (33.3%)	1	1/6 (16.7%)	1	0/3 (0%)	0	9/76 (11.8%)	10	0/3 (0%)	0	2/3 (66.7%)	6	1/1 (100%)	1	0/3 (0%)	0	4/17 (23.5%)	5	1/14 (7.1%)	1
Dyspnoea exertional	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	3/76 (3.9%)	3	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Epistaxis	0/3 (0%)	0	1/4 (25%)	1	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	4	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	2	1/14 (7.1%)	1
Increased bronchial secretion	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Nasal congestion	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	3	0/14 (0%)	0
Nasal polyps	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Obstructive airways disorder	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Oropharyngeal pain	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	3	1/3 (33.3%)	1	2/3 (66.7%)	4	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Paranasal sinus hypersecretion	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	2/14 (14.3%)	2
Pleural effusion	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Pleuritic pain	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Pneumothorax	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Productive cough	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	5	1/14 (7.1%)	1
Pulmonary alveolar haemorrhage	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Pulmonary hypertension	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/17 (0%)	0	0/14 (0%)	0
Rhinorrhoea	0/3 (0%)	0	1/4 (25%)	1	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	1/14 (7.1%)	1
Sinus congestion	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	4/76 (5.3%)	4	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Sneezing	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Sputum discoloured	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Throat tightness	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Upper-airway cough syndrome	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	4	1/14 (7.1%)	2
Wheezing	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	1/3 (33.3%)	6	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	2	0/14 (0%)	0
Skin and subcutaneous tissue disorders
Actinic keratosis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Alopecia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Blister	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	2	0/14 (0%)	0
Dermatitis allergic	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Dry skin	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	1/14 (7.1%)	1
Ecchymosis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Eczema	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	2	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Erythema	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	3	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Erythema annulare	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Hyperhidrosis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	5/76 (6.6%)	5	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Ingrowing nail	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Macule	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/17 (0%)	0	0/14 (0%)	0
Miliaria	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Night sweats	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	6/76 (7.9%)	7	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Petechiae	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Pruritus	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	7/76 (9.2%)	11	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	2	0/14 (0%)	0
Purpura	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Rash	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	11/76 (14.5%)	19	1/3 (33.3%)	1	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	3/17 (17.6%)	4	0/14 (0%)	0
Rash erythematous	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Rash macular	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Rash maculo-papular	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	2/14 (14.3%)	3
Rash pruritic	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1
Scab	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Skin exfoliation	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Skin irritation	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/17 (0%)	0	0/14 (0%)	0
Skin lesion	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	4	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Solar lentigo	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	2	0/14 (0%)	0
Swelling face	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Urticaria	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Social circumstances
Ex-tobacco user	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Vascular disorders
Deep vein thrombosis	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Flushing	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	0/14 (0%)	0
Haematoma	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	4/76 (5.3%)	5	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/17 (5.9%)	1	1/14 (7.1%)	1
Hot flush	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/76 (1.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	2/14 (14.3%)	2
Hypertension	2/3 (66.7%)	2	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	8/76 (10.5%)	8	0/3 (0%)	0	2/3 (66.7%)	5	0/1 (0%)	0	0/3 (0%)	0	2/17 (11.8%)	4	1/14 (7.1%)	2
Hypotension	1/3 (33.3%)	1	3/4 (75%)	3	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	3/76 (3.9%)	3	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	1	0/3 (0%)	0	2/17 (11.8%)	2	1/14 (7.1%)	1
Orthostatic hypotension	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Phlebitis	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Systolic hypertension	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/76 (2.6%)	3	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	0/14 (0%)	0
Thrombophlebitis superficial	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/76 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/17 (0%)	0	1/14 (7.1%)	1

Limitations/Caveats

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Principal Investigators are NOT employed by the organization sponsoring the study.

Medimmune has 60 days to review results communications prior to public release and may delete information that compromises on-going studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.