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)
136
Enrollment
21
Locations
12
Arms
107.1
Actual Duration (Months)
6.5
Patients Per Site
0.1
Patients Per Site Per Month

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 DiseaseIntervention/TreatmentPhase
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

ArmIntervention/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

SiteCityStateCountryPostal Code
1Research SiteBirminghamAlabamaUnited States35249
2Research SiteLa JollaCaliforniaUnited States92093
3Research SiteWashingtonDistrict of ColumbiaUnited States20007
4Research SiteTampaFloridaUnited States33612
5Research SiteChicagoIllinoisUnited States60612
6Research SiteWestwoodKansasUnited States66205
7Research SiteRochesterMinnesotaUnited States55905
8Research SiteNew BrunswickNew JerseyUnited States08903
9Research SiteLake SuccessNew YorkUnited States11042
10Research SiteHersheyPennsylvaniaUnited States17033
11Research SiteHoustonTexasUnited States77030
12Research SiteMorgantownWest VirginiaUnited States26506
13Research SiteMilwaukeeWisconsinUnited States53226
14Research SiteGentBelgium9000
15Research SiteLeuvenBelgium3000
16Research SiteYvoirBelgium5530
17Research SiteMontrealQuebecCanadaH3T 1E2
18Research SiteConaItaly44124
19Research SiteModenaItaly41124
20Research SiteMadridSpain28033
21Research SiteMadridSpain28050

Sponsors and Collaborators

  • MedImmune LLC

Investigators

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

Study Documents (Full-Text)

More Information

Additional Information:

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
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment DetailA 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kgPart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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
STARTED343637633131714
COMPLETED000109010063
NOT COMPLETED343536732131111

Baseline Characteristics

Arm/Group TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kgPart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kgTOTAL
Arm/Group DescriptionParticipants 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 Participants343637633131714136
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
TitleOptimal Biologic Dose of MEDI-551 for Part A
DescriptionOptimal 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 FrameDay 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 TitlePart A-MEDI-551 Part A
Arm/Group DescriptionParticipants 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 Participants95
Number [mg/Kg]
12
2. Primary Outcome
TitleHighest Protocol-defined Dose for Part B
DescriptionHighest 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 FrameDay 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 TitlePart B-MEDI-551
Arm/Group DescriptionParticipants 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 Participants7
Number [mg/Kg]
24
3. Primary Outcome
TitleHighest Protocol-defined Dose for Part C
DescriptionHighest 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 FrameDay 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 TitlePart C-MEDI-551 + Rituximab
Arm/Group DescriptionParticipants 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 Participants20
Number [mg/kg]
12
4. Primary Outcome
TitleNumber of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Part A, Part B, and Part C
DescriptionAn 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 FrameDay 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kgPart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + Rituximab
Arm/Group DescriptionParticipants 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 Participants3436376331317
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
TitleNumber of Participants With Dose Limiting Toxicities of MEDI-551 in Part A, Part B, and Part C
DescriptionA 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 FrameDay 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kgPart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + Rituximab
Arm/Group DescriptionParticipants 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 Participants3436376331317
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
TitleNumber of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part A, Part B, and Part C
DescriptionNumber 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 FrameDay 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kgPart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + Rituximab
Arm/Group DescriptionParticipants 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 Participants3436376331317
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
TitleNumber of Participants With Abnormal Vital Signs Reported as TEAEs in Part A, Part B, and Part C
DescriptionNumber 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 FrameDay 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kgPart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + Rituximab
Arm/Group DescriptionParticipants 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 Participants3436376331317
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
TitleNumber of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part A, Part B, and Part C
DescriptionNumber 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 FrameDay 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kgPart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + Rituximab
Arm/Group DescriptionParticipants 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 Participants3436376331317
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
TitlePercentage of Participants With Complete Response for Part B, Part C, and Part D
DescriptionComplete 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 FrameDay 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 TitlePart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants33031613
Number (95% Confidence Interval) [Percentage of Participants]
33.3
1110%
0
0%
33.3
1110%
18.8
313.3%
0
0%
10. Primary Outcome
TitlePercentage of Participants With Partial Response for Part B, Part C, and Part D
DescriptionThe 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 FrameDay 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 TitlePart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants33031613
Number [Percentage of Participants]
33.3
1110%
33.3
832.5%
33.3
1110%
25.0
416.7%
23.1
770%
11. Primary Outcome
TitleDuration of Complete Response for Part B, Part C, and Part D
DescriptionDuration 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 FrameDay 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 TitlePart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants100130
Median (Full Range) [Months]
NA
NA
NA
12. Primary Outcome
TitlePercentage of Participants With Objective Response Rate for Part B, Part C, and Part D
DescriptionObjective 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 FrameDay 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 TitlePart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants33031613
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
TitleDuration of Objective Response for Part B, Part C, and Part D
DescriptionDuration 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 FrameCycle 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 TitlePart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants210273
Median (Full Range) [Months]
NA
27.5
3.7
NA
3.7
14. Primary Outcome
TitlePercentage of Participants With Disease Control Rate for Part B, Part C, and Part D
DescriptionDisease 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 FrameDay 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 TitlePart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants3303116
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
TitleDuration of Disease Control for Part B, Part C, and Part D
DescriptionDuration 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 FrameDay 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 TitlePart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants3303116
Median (Full Range) [Months]
NA
29.8
5.5
14.6
3.8
16. Primary Outcome
TitleTime to Response for Part B, Part C, and Part D
DescriptionTime 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 FrameDay 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 TitlePart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants210273
Median (Full Range) [Months]
6.5
12.0
1.8
2.0
1.8
17. Primary Outcome
TitleProgression Free Survival for Part B, Part C, and Part D
DescriptionProgression-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 FrameDay 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 TitlePart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants33031613
Median (Full Range) [Months]
NA
29.8
5.5
3.5
2.0
18. Primary Outcome
TitleOverall Survival for Part B, Part C, and Part D
DescriptionOverall 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 FrameDay 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 TitlePart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants33031613
Median (Full Range) [Months]
NA
NA
25.0
33.4
17.9
19. Secondary Outcome
TitleNumber of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Part D
DescriptionAn 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 FrameDay 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 TitlePart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants14
TEAEs
14
466.7%
TESAEs
5
166.7%
20. Secondary Outcome
TitleNumber of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part D
DescriptionNumber 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 FrameDay 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 TitlePart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants14
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
TitleNumber of Participants With Abnormal Vital Signs Reported as TEAEs in Part D
DescriptionNumber 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 FrameDay 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 TitlePart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants14
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
TitleNumber of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part D
DescriptionNumber 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 FrameDay 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 TitlePart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants14
Count of Participants [Participants]
1
33.3%
23. Secondary Outcome
TitlePercentage of Participants With Complete Response for Part A
DescriptionThe 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 FrameDay 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants3435372
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
TitlePercentage of Participants With Partial Response for Part A
DescriptionThe 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 FrameDay 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants3435372
Number [Percentage of Participants]
33.3
1110%
0
0%
0
0%
0
0%
33.3
1110%
15.3
20.1%
25. Secondary Outcome
TitleDuration of Complete Response for Part A
DescriptionDuration 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 FrameDay 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants100109
Median (Full Range) [Months]
7.1
14.9
14.3
26. Secondary Outcome
TitlePercentage of Participants With Objective Response Rate for Part A
DescriptionThe 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 FrameDay 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants3435372
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
TitleDuration of Objective Response for Part A
DescriptionThe 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 FrameDay 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants2001120
Median (Full Range) [Months]
8.8
15.0
3.0
19.8
28. Secondary Outcome
TitlePercentage of Participants With Disease Control Rate for Part A
DescriptionDisease 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 FrameDay 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants3435372
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
TitleDuration of Disease Control for Part A
DescriptionDuration 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 FrameDay 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants2224253
Median (Full Range) [Months]
12.6
NA
NA
10.9
6.6
18.0
30. Secondary Outcome
TitleTime to Response for Part A
DescriptionThe 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 FrameDay 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants2001120
Median (Full Range) [Months]
3.7
1.9
3.6
3.2
31. Secondary Outcome
TitleProgression Free Survival for Part A
DescriptionThe 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 FrameDay 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants3435372
Median (Full Range) [Months]
12.6
5.9
3.5
4.9
6.6
11.3
32. Secondary Outcome
TitleOverall Survival for Part A
DescriptionThe 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 FrameDay 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants3435372
Median (Full Range) [Months]
NA
44.6
9.9
NA
8.1
45.3
33. Secondary Outcome
TitleTrough Serum Concentration of MEDI-551 by Treatment Cycle
DescriptionTrough 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 FrameFor 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kgPart A-MEDI-551 12 mg/kg (Expansion)Part B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants3436366733131714
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
TitlePeak Serum Concentration of MEDI-551 by Treatment Cycle
DescriptionPeak 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 FrameFor 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kgPart A-MEDI-551 12 mg/kg (Expansion)Part B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants3436366733131714
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
TitleArea Under the Concentration Curve at Steady State (AUCss) of MEDI-551
DescriptionArea under the concentration-time curve at steady state (Css, AUC) of MEDI-551 is reported.
Time FramePart 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kgPart A-MEDI-551 12 mg/kg (Expansion)Part B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants3436366733131714
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
TitleApparent Clearance of MEDI-551
DescriptionApparent clearance of MEDI-551 is reported.
Time FramePart 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kgPart A-MEDI-551 12 mg/kg (Expansion)Part B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants3436366733131714
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
TitleVolume of Distribution of MEDI-551
DescriptionVolume 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 FramePart 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kgPart A-MEDI-551 12 mg/kg (Expansion)Part B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants3436366733131714
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
TitleTerminal Half-life (t1/2) of MEDI-551
DescriptionTerminal half-life is the time required for the plasma concentration of MEDI-551 to fall by 50% during the terminal phase.
Time FramePart 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kgPart A-MEDI-551 12 mg/kg (Expansion)Part B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants3436366733131714
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
TitleNumber of Participants With Positive Anti-drug Antibodies (ADA) Titer to MEDI-551
DescriptionNumber of participants with positive Anti-drug antibodies (ADA) titer to MEDI-551 is reported.
Time FramePart 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kgPart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants34363763331714
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
TitleB-cell Concentration in Serum
DescriptionB-cell Concentration in serum is reported.
Time FramePart 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kgPart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants000000000000
41. Secondary Outcome
TitleImmunoglobulin (Ig) Concentration in Serum
DescriptionImmunoglobin (Ig) concentration in serum is reported.
Time FramePart 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 TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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 Participants3436376
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 FrameDay 1 through 90-Day Post Last Dose (Approximately 9 years)
Adverse Event Reporting Description
Arm/Group TitlePart A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kgPart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Arm/Group DescriptionParticipants 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/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kgPart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/3 (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/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kgPart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total1/3 (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
Anaemia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Febrile neutropenia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Neutropenia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Cardiac disorders
Sinus bradycardia0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Gastrointestinal disorders
Abdominal pain0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Abdominal pain upper0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Faecaloma0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Nausea0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Pancreatitis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Vomiting0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
General disorders
General physical health deterioration0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Non-cardiac chest pain0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Pyrexia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 03/76 (3.9%) 40/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Hepatobiliary disorders
Acute hepatic failure0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Cholecystitis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Infections and infestations
Abscess limb0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Bacteraemia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Bronchitis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 01/17 (5.9%) 21/14 (7.1%) 1
Gastroenteritis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 11/3 (33.3%) 10/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Lung infection0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Pneumonia0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 02/76 (2.6%) 30/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 01/17 (5.9%) 12/14 (14.3%) 2
Sepsis syndrome0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Septic shock0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Sinusitis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Staphylococcal sepsis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Varicella0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Injury, poisoning and procedural complications
Fall0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Infusion related reaction0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 60/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Procedural haemorrhage0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Procedural pain0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Spinal compression fracture0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Subarachnoid haemorrhage0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Metabolism and nutrition disorders
Dehydration0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 11/14 (7.1%) 1
Hypercalcaemia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Musculoskeletal and connective tissue disorders
Back pain1/3 (33.3%) 10/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Intervertebral disc protrusion0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Lumbar spinal stenosis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Musculoskeletal chest pain1/3 (33.3%) 10/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 01/1 (100%) 10/3 (0%) 00/17 (0%) 00/14 (0%) 0
Osteolysis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Adenocarcinoma of colon0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
B-cell lymphoma0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 01/3 (33.3%) 10/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Diffuse large b-cell lymphoma0/3 (0%) 00/4 (0%) 01/3 (33.3%) 10/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 02/17 (11.8%) 20/14 (0%) 0
Malignant melanoma0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 01/3 (33.3%) 10/17 (0%) 00/14 (0%) 0
Non-hodgkin's lymphoma0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Polycythaemia vera0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Squamous cell carcinoma0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Nervous system disorders
Cauda equina syndrome0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Syncope0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Toxic encephalopathy0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Psychiatric disorders
Confusional state0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Mental status changes0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Renal and urinary disorders
Acute kidney injury0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Dysuria0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Respiratory, thoracic and mediastinal disorders
Bronchiectasis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Dyspnoea0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Pneumothorax0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Pulmonary embolism0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Pulmonary haemorrhage0/3 (0%) 00/4 (0%) 01/3 (33.3%) 10/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Respiratory failure0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Skin and subcutaneous tissue disorders
Pemphigoid0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Vascular disorders
Deep vein thrombosis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 01/1 (100%) 10/3 (0%) 00/17 (0%) 00/14 (0%) 0
Haematoma0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Hypotension0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Shock haemorrhagic0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Other (Not Including Serious) Adverse Events
Part A-MEDI-551 0.5 mg/kgPart A-MEDI-551 1 mg/kgPart A-MEDI-551 2 mg/kgPart A-MEDI-551 4 mg/kgPart A-MEDI-551 8 mg/kgPart A-MEDI-551 12 mg/kgPart B-MEDI-551 6 mg/kgPart B-MEDI-551 12 mg/kgPart B-MEDI-551 24 mg/kgPart C-MEDI-551 8 mg/kg + RituximabPart C-MEDI-551 12 mg/kg + RituximabPart D-MEDI-551 12 mg/kg
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total3/3 (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
Anaemia0/3 (0%) 02/4 (50%) 20/3 (0%) 00/6 (0%) 01/3 (33.3%) 16/76 (7.9%) 80/3 (0%) 01/3 (33.3%) 11/1 (100%) 20/3 (0%) 04/17 (23.5%) 182/14 (14.3%) 3
Febrile neutropenia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Hypergammaglobulinaemia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 01/3 (33.3%) 10/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Increased tendency to bruise0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Leukocytosis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Leukopenia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 01/3 (33.3%) 50/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Lymph node pain0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 20/14 (0%) 0
Lymphopenia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Neutropenia0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 11/3 (33.3%) 113/76 (17.1%) 191/3 (33.3%) 11/3 (33.3%) 130/1 (0%) 01/3 (33.3%) 12/17 (11.8%) 71/14 (7.1%) 2
Polycythaemia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Splenomegaly0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Thrombocytopenia0/3 (0%) 01/4 (25%) 10/3 (0%) 03/6 (50%) 70/3 (0%) 06/76 (7.9%) 70/3 (0%) 01/3 (33.3%) 20/1 (0%) 00/3 (0%) 02/17 (11.8%) 192/14 (14.3%) 4
Cardiac disorders
Angina pectoris0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Atrial fibrillation0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 03/76 (3.9%) 30/3 (0%) 01/3 (33.3%) 20/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Atrial flutter0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 20/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Atrial tachycardia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 30/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Bradycardia1/3 (33.3%) 10/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Cardiac failure chronic0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Mitral valve incompetence0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 01/3 (33.3%) 10/17 (0%) 00/14 (0%) 0
Palpitations0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 21/14 (7.1%) 1
Supraventricular tachycardia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Tachycardia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 06/76 (7.9%) 71/3 (33.3%) 10/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 21/14 (7.1%) 1
Ear and labyrinth disorders
Cerumen impaction1/3 (33.3%) 10/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 01/3 (33.3%) 10/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Deafness0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Ear pain0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 03/76 (3.9%) 31/3 (33.3%) 10/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 20/14 (0%) 0
Ear swelling0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Excessive cerumen production1/3 (33.3%) 10/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Hypoacusis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Otorrhoea0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 01/3 (33.3%) 10/17 (0%) 00/14 (0%) 0
Vertigo0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 2
Endocrine disorders
Hypothyroidism0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Eye disorders
Cataract0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Dry eye0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Exophthalmos0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Eye pruritus0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Glaucoma0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Ocular hyperaemia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Vision blurred0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 01/1 (100%) 10/3 (0%) 00/17 (0%) 00/14 (0%) 0
Gastrointestinal disorders
Abdominal discomfort0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 30/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Abdominal distension0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 03/76 (3.9%) 30/3 (0%) 01/3 (33.3%) 40/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Abdominal pain0/3 (0%) 02/4 (50%) 30/3 (0%) 00/6 (0%) 01/3 (33.3%) 16/76 (7.9%) 70/3 (0%) 01/3 (33.3%) 20/1 (0%) 00/3 (0%) 02/17 (11.8%) 31/14 (7.1%) 1
Abdominal pain lower0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 01/3 (33.3%) 21/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Abdominal pain upper0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 04/76 (5.3%) 40/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Anal incontinence0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Constipation0/3 (0%) 01/4 (25%) 50/3 (0%) 00/6 (0%) 00/3 (0%) 010/76 (13.2%) 121/3 (33.3%) 11/3 (33.3%) 30/1 (0%) 01/3 (33.3%) 16/17 (35.3%) 72/14 (14.3%) 2
Dental caries0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Diarrhoea3/3 (100%) 102/4 (50%) 41/3 (33.3%) 10/6 (0%) 00/3 (0%) 018/76 (23.7%) 211/3 (33.3%) 12/3 (66.7%) 31/1 (100%) 21/3 (33.3%) 15/17 (29.4%) 153/14 (21.4%) 4
Dry mouth0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 30/3 (0%) 00/3 (0%) 01/1 (100%) 10/3 (0%) 01/17 (5.9%) 21/14 (7.1%) 1
Dyspepsia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 03/76 (3.9%) 30/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Dysphagia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 02/17 (11.8%) 20/14 (0%) 0
Gastrooesophageal reflux disease0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 01/3 (33.3%) 11/76 (1.3%) 11/3 (33.3%) 12/3 (66.7%) 30/1 (0%) 00/3 (0%) 02/17 (11.8%) 21/14 (7.1%) 3
Gingival pain0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Impaired gastric emptying0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Inguinal hernia0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Intestinal ischaemia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Lip dry0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Nausea0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 11/3 (33.3%) 113/76 (17.1%) 160/3 (0%) 01/3 (33.3%) 10/1 (0%) 01/3 (33.3%) 25/17 (29.4%) 93/14 (21.4%) 3
Oesophageal stenosis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 01/3 (33.3%) 10/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Oral pain0/3 (0%) 00/4 (0%) 01/3 (33.3%) 10/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Salivary hypersecretion0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Stomatitis0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 02/17 (11.8%) 20/14 (0%) 0
Tongue coated0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Toothache0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Upper gastrointestinal haemorrhage0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Vomiting0/3 (0%) 01/4 (25%) 10/3 (0%) 01/6 (16.7%) 10/3 (0%) 07/76 (9.2%) 80/3 (0%) 01/3 (33.3%) 10/1 (0%) 01/3 (33.3%) 14/17 (23.5%) 60/14 (0%) 0
General disorders
Asthenia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 05/76 (6.6%) 60/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 02/17 (11.8%) 40/14 (0%) 0
Breakthrough pain0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Chills0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 05/76 (6.6%) 60/3 (0%) 01/3 (33.3%) 40/1 (0%) 00/3 (0%) 01/17 (5.9%) 12/14 (14.3%) 3
Cyst0/3 (0%) 00/4 (0%) 01/3 (33.3%) 10/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Early satiety0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 01/3 (33.3%) 10/17 (0%) 00/14 (0%) 0
Fatigue1/3 (33.3%) 11/4 (25%) 51/3 (33.3%) 12/6 (33.3%) 23/3 (100%) 328/76 (36.8%) 332/3 (66.7%) 23/3 (100%) 60/1 (0%) 01/3 (33.3%) 29/17 (52.9%) 205/14 (35.7%) 6
Gait disturbance0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 03/17 (17.6%) 31/14 (7.1%) 1
Gravitational oedema0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Ill-defined disorder0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Influenza like illness1/3 (33.3%) 10/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Infusion site pain0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Localised oedema0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Malaise0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 30/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Mass0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 01/3 (33.3%) 10/17 (0%) 00/14 (0%) 0
Medical device site bruise0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Medical device site pain0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Mucosal inflammation0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 20/14 (0%) 0
Necrosis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 20/14 (0%) 0
Non-cardiac chest pain0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 30/1 (0%) 01/3 (33.3%) 10/17 (0%) 00/14 (0%) 0
Oedema0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Oedema peripheral0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 08/76 (10.5%) 90/3 (0%) 02/3 (66.7%) 51/1 (100%) 20/3 (0%) 05/17 (29.4%) 92/14 (14.3%) 2
Pain0/3 (0%) 01/4 (25%) 10/3 (0%) 01/6 (16.7%) 10/3 (0%) 04/76 (5.3%) 40/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Performance status decreased0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Peripheral swelling0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 05/76 (6.6%) 90/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 02/17 (11.8%) 20/14 (0%) 0
Pyrexia0/3 (0%) 00/4 (0%) 01/3 (33.3%) 12/6 (33.3%) 20/3 (0%) 013/76 (17.1%) 181/3 (33.3%) 11/3 (33.3%) 40/1 (0%) 00/3 (0%) 02/17 (11.8%) 32/14 (14.3%) 2
Systemic inflammatory response syndrome0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Hepatobiliary disorders
Hyperbilirubinaemia0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 20/14 (0%) 0
Immune system disorders
Hypogammaglobulinaemia0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 20/3 (0%) 00/76 (0%) 01/3 (33.3%) 10/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Immune system disorder0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 01/3 (33.3%) 10/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Seasonal allergy0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 11/3 (33.3%) 10/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Infections and infestations
Abscess limb0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Bacterial vaginosis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Bronchitis0/3 (0%) 01/4 (25%) 11/3 (33.3%) 10/6 (0%) 00/3 (0%) 04/76 (5.3%) 62/3 (66.7%) 22/3 (66.7%) 30/1 (0%) 00/3 (0%) 01/17 (5.9%) 11/14 (7.1%) 3
Candida infection0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Cellulitis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 02/17 (11.8%) 30/14 (0%) 0
Chronic sinusitis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 01/3 (33.3%) 10/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Conjunctivitis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 03/76 (3.9%) 30/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Diverticulitis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 30/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Ear infection0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 11/3 (33.3%) 10/3 (0%) 00/1 (0%) 01/3 (33.3%) 11/17 (5.9%) 71/14 (7.1%) 1
Furuncle0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Gastroenteritis viral0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Herpes zoster0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 03/76 (3.9%) 40/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Influenza0/3 (0%) 00/4 (0%) 01/3 (33.3%) 10/6 (0%) 00/3 (0%) 00/76 (0%) 01/3 (33.3%) 10/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Laryngitis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 03/76 (3.9%) 30/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Nasopharyngitis0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 04/76 (5.3%) 50/3 (0%) 01/3 (33.3%) 20/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Oral herpes0/3 (0%) 00/4 (0%) 00/3 (0%) 02/6 (33.3%) 30/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 40/14 (0%) 0
Pharyngitis0/3 (0%) 00/4 (0%) 01/3 (33.3%) 10/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Pneumonia0/3 (0%) 00/4 (0%) 01/3 (33.3%) 10/6 (0%) 00/3 (0%) 01/76 (1.3%) 12/3 (66.7%) 30/3 (0%) 00/1 (0%) 00/3 (0%) 02/17 (11.8%) 21/14 (7.1%) 2
Pyelonephritis acute0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Rash pustular0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 01/3 (33.3%) 20/3 (0%) 00/1 (0%) 01/3 (33.3%) 10/17 (0%) 00/14 (0%) 0
Respiratory tract infection0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Rhinitis0/3 (0%) 01/4 (25%) 11/3 (33.3%) 10/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 01/3 (33.3%) 20/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Sinusitis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 04/76 (5.3%) 41/3 (33.3%) 61/3 (33.3%) 20/1 (0%) 00/3 (0%) 04/17 (23.5%) 82/14 (14.3%) 2
Tonsillitis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 01/3 (33.3%) 10/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Tooth infection0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Upper respiratory tract infection0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 09/76 (11.8%) 112/3 (66.7%) 61/3 (33.3%) 100/1 (0%) 00/3 (0%) 03/17 (17.6%) 42/14 (14.3%) 2
Urinary tract infection0/3 (0%) 00/4 (0%) 01/3 (33.3%) 20/6 (0%) 00/3 (0%) 08/76 (10.5%) 90/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 02/17 (11.8%) 30/14 (0%) 0
Viral infection0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Injury, poisoning and procedural complications
Contusion0/3 (0%) 00/4 (0%) 01/3 (33.3%) 11/6 (16.7%) 20/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 01/1 (100%) 10/3 (0%) 02/17 (11.8%) 30/14 (0%) 0
Fall0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 01/1 (100%) 20/3 (0%) 01/17 (5.9%) 11/14 (7.1%) 1
Infusion related reaction0/3 (0%) 00/4 (0%) 00/3 (0%) 02/6 (33.3%) 20/3 (0%) 034/76 (44.7%) 1081/3 (33.3%) 62/3 (66.7%) 81/1 (100%) 10/3 (0%) 01/17 (5.9%) 14/14 (28.6%) 12
Laceration0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 30/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Limb injury0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Post-traumatic pain1/3 (33.3%) 10/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Procedural complication0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Procedural pain0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 03/76 (3.9%) 30/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Rib fracture0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 01/1 (100%) 10/3 (0%) 00/17 (0%) 00/14 (0%) 0
Skin abrasion0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Vascular access complication0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Wrong drug administered0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Investigations
Activated partial thromboplastin time prolonged0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 20/14 (0%) 0
Alanine aminotransferase increased0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 03/76 (3.9%) 30/3 (0%) 00/3 (0%) 01/1 (100%) 20/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Aspartate aminotransferase increased0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 04/76 (5.3%) 40/3 (0%) 00/3 (0%) 01/1 (100%) 30/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Blood albumin decreased0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 20/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Blood alkaline phosphatase increased0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 01/1 (100%) 20/3 (0%) 02/17 (11.8%) 41/14 (7.1%) 1
Blood bilirubin increased0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Blood chloride decreased0/3 (0%) 01/4 (25%) 20/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Blood cholesterol increased0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Blood creatinine increased0/3 (0%) 00/4 (0%) 01/3 (33.3%) 10/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 01/3 (33.3%) 11/1 (100%) 10/3 (0%) 02/17 (11.8%) 20/14 (0%) 0
Blood fibrinogen decreased0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Blood fibrinogen increased0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 01/3 (33.3%) 20/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Blood immunoglobulin m decreased0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Blood iron decreased0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Blood lactate dehydrogenase increased0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 30/3 (0%) 00/3 (0%) 01/1 (100%) 10/3 (0%) 01/17 (5.9%) 11/14 (7.1%) 1
Blood phosphorus decreased0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Blood potassium decreased0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 2
Blood triglycerides increased1/3 (33.3%) 50/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Blood urea increased0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
C-reactive protein increased0/3 (0%) 01/4 (25%) 11/3 (33.3%) 10/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 01/3 (33.3%) 50/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Electrocardiogram qt prolonged0/3 (0%) 00/4 (0%) 01/3 (33.3%) 10/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 11/14 (7.1%) 1
Gamma-glutamyltransferase increased0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 03/76 (3.9%) 40/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Glucose urine present0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Haematocrit decreased0/3 (0%) 01/4 (25%) 20/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Karnofsky scale worsened0/3 (0%) 00/4 (0%) 01/3 (33.3%) 10/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Low density lipoprotein increased0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Lymphocyte count decreased0/3 (0%) 01/4 (25%) 40/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 01/1 (100%) 110/3 (0%) 02/17 (11.8%) 73/14 (21.4%) 3
Mean cell volume increased0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Neutrophil count abnormal0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Neutrophil count decreased1/3 (33.3%) 21/4 (25%) 50/3 (0%) 01/6 (16.7%) 40/3 (0%) 05/76 (6.6%) 70/3 (0%) 01/3 (33.3%) 31/1 (100%) 10/3 (0%) 02/17 (11.8%) 24/14 (28.6%) 4
Occult blood positive0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Platelet count decreased0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 30/3 (0%) 01/3 (33.3%) 11/1 (100%) 10/3 (0%) 01/17 (5.9%) 11/14 (7.1%) 1
Prostatic specific antigen increased0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Protein total decreased0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 20/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Red blood cell count decreased0/3 (0%) 01/4 (25%) 20/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Serum ferritin decreased0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Vitamin d decreased0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Weight decreased0/3 (0%) 00/4 (0%) 01/3 (33.3%) 10/6 (0%) 00/3 (0%) 03/76 (3.9%) 30/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 01/17 (5.9%) 11/14 (7.1%) 1
Weight increased0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 02/17 (11.8%) 50/14 (0%) 0
White blood cell count decreased0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 11/3 (33.3%) 13/76 (3.9%) 40/3 (0%) 02/3 (66.7%) 41/1 (100%) 80/3 (0%) 02/17 (11.8%) 43/14 (21.4%) 4
Metabolism and nutrition disorders
Decreased appetite0/3 (0%) 02/4 (50%) 21/3 (33.3%) 11/6 (16.7%) 10/3 (0%) 07/76 (9.2%) 70/3 (0%) 01/3 (33.3%) 11/1 (100%) 10/3 (0%) 02/17 (11.8%) 25/14 (35.7%) 6
Dehydration0/3 (0%) 01/4 (25%) 20/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Hypercalcaemia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 03/76 (3.9%) 30/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Hyperglycaemia0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 01/76 (1.3%) 70/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 02/17 (11.8%) 42/14 (14.3%) 2
Hyperkalaemia0/3 (0%) 02/4 (50%) 60/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Hypernatraemia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 01/1 (100%) 20/3 (0%) 02/17 (11.8%) 30/14 (0%) 0
Hypertriglyceridaemia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 04/76 (5.3%) 50/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Hyperuricaemia1/3 (33.3%) 21/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 40/3 (0%) 00/3 (0%) 01/1 (100%) 20/3 (0%) 01/17 (5.9%) 12/14 (14.3%) 2
Hypoalbuminaemia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 01/1 (100%) 30/3 (0%) 02/17 (11.8%) 60/14 (0%) 0
Hypocalcaemia0/3 (0%) 02/4 (50%) 20/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 11/1 (100%) 20/3 (0%) 02/17 (11.8%) 21/14 (7.1%) 1
Hypoglycaemia0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Hypokalaemia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 01/17 (5.9%) 52/14 (14.3%) 2
Hypomagnesaemia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 01/3 (33.3%) 20/1 (0%) 00/3 (0%) 01/17 (5.9%) 50/14 (0%) 0
Hyponatraemia0/3 (0%) 01/4 (25%) 60/3 (0%) 01/6 (16.7%) 20/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 02/17 (11.8%) 60/14 (0%) 0
Hypophosphataemia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 02/17 (11.8%) 30/14 (0%) 0
Vitamin d deficiency0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Musculoskeletal and connective tissue disorders
Arthralgia1/3 (33.3%) 10/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 06/76 (7.9%) 90/3 (0%) 02/3 (66.7%) 50/1 (0%) 01/3 (33.3%) 13/17 (17.6%) 60/14 (0%) 0
Arthritis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Back pain1/3 (33.3%) 22/4 (50%) 20/3 (0%) 00/6 (0%) 01/3 (33.3%) 211/76 (14.5%) 120/3 (0%) 02/3 (66.7%) 40/1 (0%) 02/3 (66.7%) 24/17 (23.5%) 52/14 (14.3%) 6
Bone pain0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 03/76 (3.9%) 50/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 02/17 (11.8%) 20/14 (0%) 0
Bursitis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Groin pain0/3 (0%) 01/4 (25%) 10/3 (0%) 01/6 (16.7%) 10/3 (0%) 02/76 (2.6%) 31/3 (33.3%) 11/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Inguinal mass0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Joint swelling0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Muscle spasms0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 01/3 (33.3%) 19/76 (11.8%) 111/3 (33.3%) 10/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 12/14 (14.3%) 3
Muscular weakness0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 01/1 (100%) 10/3 (0%) 02/17 (11.8%) 20/14 (0%) 0
Musculoskeletal chest pain0/3 (0%) 01/4 (25%) 11/3 (33.3%) 10/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 01/3 (33.3%) 21/1 (100%) 10/3 (0%) 00/17 (0%) 00/14 (0%) 0
Musculoskeletal pain0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 03/76 (3.9%) 30/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 02/17 (11.8%) 51/14 (7.1%) 2
Musculoskeletal stiffness0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 20/14 (0%) 0
Myalgia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 04/76 (5.3%) 40/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 02/17 (11.8%) 30/14 (0%) 0
Osteoarthritis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Osteonecrosis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Pain in extremity1/3 (33.3%) 10/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 06/76 (7.9%) 91/3 (33.3%) 11/3 (33.3%) 20/1 (0%) 00/3 (0%) 05/17 (29.4%) 60/14 (0%) 0
Pain in jaw0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 01/3 (33.3%) 20/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Sarcopenia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Spondylitis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Benign neoplasm of thyroid gland0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Bowen's disease0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 21/3 (33.3%) 10/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Haemangioma0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Melanocytic naevus0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Metastatic lymphoma0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Seborrhoeic keratosis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 02/17 (11.8%) 20/14 (0%) 0
Skin papilloma0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 20/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Squamous cell carcinoma0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 20/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 01/17 (5.9%) 20/14 (0%) 0
Squamous cell carcinoma of skin0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 11/3 (33.3%) 11/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Tumour pain0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Nervous system disorders
Amnesia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Anosmia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Cerebrovascular accident0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 01/1 (100%) 10/3 (0%) 00/17 (0%) 00/14 (0%) 0
Dizziness0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 010/76 (13.2%) 120/3 (0%) 00/3 (0%) 01/1 (100%) 10/3 (0%) 01/17 (5.9%) 23/14 (21.4%) 4
Dysgeusia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Headache0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 01/3 (33.3%) 115/76 (19.7%) 200/3 (0%) 01/3 (33.3%) 70/1 (0%) 00/3 (0%) 03/17 (17.6%) 30/14 (0%) 0
Hypersomnia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Hypoaesthesia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 04/76 (5.3%) 40/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Memory impairment0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Neuropathy peripheral2/3 (66.7%) 21/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 01/3 (33.3%) 11/17 (5.9%) 10/14 (0%) 0
Paraesthesia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 03/76 (3.9%) 40/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 20/14 (0%) 0
Peripheral sensory neuropathy0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 01/3 (33.3%) 11/3 (33.3%) 10/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Presyncope0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Sciatica0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 01/3 (33.3%) 20/3 (0%) 00/1 (0%) 00/3 (0%) 02/17 (11.8%) 30/14 (0%) 0
Seizure0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Sinus headache0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Somnolence0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Syncope0/3 (0%) 00/4 (0%) 01/3 (33.3%) 10/6 (0%) 00/3 (0%) 02/76 (2.6%) 30/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Tremor0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Product Issues
Device dislocation0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Psychiatric disorders
Aggression0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Agitation0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 11/14 (7.1%) 1
Anxiety0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 08/76 (10.5%) 80/3 (0%) 01/3 (33.3%) 10/1 (0%) 01/3 (33.3%) 12/17 (11.8%) 41/14 (7.1%) 1
Confusional state1/3 (33.3%) 10/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 02/17 (11.8%) 22/14 (14.3%) 2
Depressed mood1/3 (33.3%) 10/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Depression0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 03/76 (3.9%) 30/3 (0%) 00/3 (0%) 00/1 (0%) 01/3 (33.3%) 13/17 (17.6%) 31/14 (7.1%) 1
Hallucination0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Hallucinations, mixed0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Insomnia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 08/76 (10.5%) 80/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 02/17 (11.8%) 54/14 (28.6%) 4
Mental status changes0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Sleep disorder0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Renal and urinary disorders
Bladder spasm0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Dysuria0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Haematuria0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 02/17 (11.8%) 20/14 (0%) 0
Haemoglobinuria0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 30/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Hydronephrosis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 02/17 (11.8%) 20/14 (0%) 0
Micturition urgency0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Pollakiuria0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Urinary incontinence0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 11/14 (7.1%) 1
Urinary retention0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Urine flow decreased0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Reproductive system and breast disorders
Breast swelling0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Erectile dysfunction0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 01/3 (33.3%) 10/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Haematospermia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Nipple disorder0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Respiratory, thoracic and mediastinal disorders
Cough1/3 (33.3%) 12/4 (50%) 30/3 (0%) 00/6 (0%) 00/3 (0%) 026/76 (34.2%) 311/3 (33.3%) 13/3 (100%) 70/1 (0%) 00/3 (0%) 03/17 (17.6%) 32/14 (14.3%) 5
Dry throat0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Dyspnoea0/3 (0%) 01/4 (25%) 11/3 (33.3%) 11/6 (16.7%) 10/3 (0%) 09/76 (11.8%) 100/3 (0%) 02/3 (66.7%) 61/1 (100%) 10/3 (0%) 04/17 (23.5%) 51/14 (7.1%) 1
Dyspnoea exertional0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 03/76 (3.9%) 30/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Epistaxis0/3 (0%) 01/4 (25%) 11/3 (33.3%) 10/6 (0%) 00/3 (0%) 03/76 (3.9%) 40/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 21/14 (7.1%) 1
Increased bronchial secretion0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Nasal congestion0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 01/76 (1.3%) 10/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 01/17 (5.9%) 30/14 (0%) 0
Nasal polyps0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Obstructive airways disorder0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Oropharyngeal pain1/3 (33.3%) 10/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 03/76 (3.9%) 31/3 (33.3%) 12/3 (66.7%) 40/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Paranasal sinus hypersecretion0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 21/3 (33.3%) 10/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 02/14 (14.3%) 2
Pleural effusion0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Pleuritic pain0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Pneumothorax0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Productive cough0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 51/14 (7.1%) 1
Pulmonary alveolar haemorrhage0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Pulmonary hypertension0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 01/3 (33.3%) 10/17 (0%) 00/14 (0%) 0
Rhinorrhoea0/3 (0%) 01/4 (25%) 11/3 (33.3%) 10/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 01/3 (33.3%) 20/1 (0%) 00/3 (0%) 01/17 (5.9%) 11/14 (7.1%) 1
Sinus congestion0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 04/76 (5.3%) 41/3 (33.3%) 10/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Sneezing0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Sputum discoloured0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Throat tightness1/3 (33.3%) 10/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Upper-airway cough syndrome0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 11/3 (33.3%) 10/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 41/14 (7.1%) 2
Wheezing0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 01/3 (33.3%) 60/1 (0%) 00/3 (0%) 01/17 (5.9%) 20/14 (0%) 0
Skin and subcutaneous tissue disorders
Actinic keratosis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Alopecia0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 01/3 (33.3%) 11/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Blister0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 20/14 (0%) 0
Dermatitis allergic0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Dry skin0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 11/14 (7.1%) 1
Ecchymosis0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Eczema0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 20/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Erythema0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 03/76 (3.9%) 30/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Erythema annulare0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Hyperhidrosis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 05/76 (6.6%) 50/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Ingrowing nail0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Macule0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 01/3 (33.3%) 10/17 (0%) 00/14 (0%) 0
Miliaria0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 01/3 (33.3%) 10/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Night sweats0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 06/76 (7.9%) 70/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Petechiae0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Pruritus0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 07/76 (9.2%) 110/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 01/17 (5.9%) 20/14 (0%) 0
Purpura0/3 (0%) 00/4 (0%) 00/3 (0%) 01/6 (16.7%) 10/3 (0%) 01/76 (1.3%) 10/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Rash0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 011/76 (14.5%) 191/3 (33.3%) 11/3 (33.3%) 10/1 (0%) 00/3 (0%) 03/17 (17.6%) 40/14 (0%) 0
Rash erythematous1/3 (33.3%) 10/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Rash macular0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Rash maculo-papular0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 01/3 (33.3%) 10/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 02/14 (14.3%) 3
Rash pruritic0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1
Scab0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 01/3 (33.3%) 10/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Skin exfoliation0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Skin irritation0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 01/3 (33.3%) 10/17 (0%) 00/14 (0%) 0
Skin lesion0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 03/76 (3.9%) 40/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Solar lentigo0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 20/14 (0%) 0
Swelling face0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 01/3 (33.3%) 11/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Urticaria0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Social circumstances
Ex-tobacco user0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Vascular disorders
Deep vein thrombosis0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Flushing0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 20/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 10/14 (0%) 0
Haematoma0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 04/76 (5.3%) 50/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 01/17 (5.9%) 11/14 (7.1%) 1
Hot flush0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 01/76 (1.3%) 10/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 02/14 (14.3%) 2
Hypertension2/3 (66.7%) 21/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 08/76 (10.5%) 80/3 (0%) 02/3 (66.7%) 50/1 (0%) 00/3 (0%) 02/17 (11.8%) 41/14 (7.1%) 2
Hypotension1/3 (33.3%) 13/4 (75%) 31/3 (33.3%) 10/6 (0%) 00/3 (0%) 03/76 (3.9%) 30/3 (0%) 00/3 (0%) 01/1 (100%) 10/3 (0%) 02/17 (11.8%) 21/14 (7.1%) 1
Orthostatic hypotension0/3 (0%) 00/4 (0%) 01/3 (33.3%) 10/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Phlebitis0/3 (0%) 01/4 (25%) 10/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Systolic hypertension0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 02/76 (2.6%) 30/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 00/14 (0%) 0
Thrombophlebitis superficial0/3 (0%) 00/4 (0%) 00/3 (0%) 00/6 (0%) 00/3 (0%) 00/76 (0%) 00/3 (0%) 00/3 (0%) 00/1 (0%) 00/3 (0%) 00/17 (0%) 01/14 (7.1%) 1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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.

Results Point of Contact

Name/TitleShahram Rahimian
OrganizationMedImmune, LLC
Phone800-236-9933
Emailinformation.center@astrazeneca.com
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