A Phase 1, Dose-escalation Study of MEDI-551 in Japanese Adult Patients With Relapsed or Refractory Advanced B-cell Malignancies

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01957579
• Collaborator: MedImmune LLC (Industry)
• Enrollment: 32
• Locations: 3
• Arm: 1
• Actual Duration (Months): 51.7
• Patients Per Site: 10.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the safety and tolerability of MEDI-551 in Japanese patients with relapsed or refractory advanced B-cell malignancies.

Condition or Disease	Intervention/Treatment	Phase
Blood Cancer; Advanced B Cell Malignancies	Drug: MEDI-551	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 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 Japanese Adult Patients With Relapsed or Refractory Advanced B-cell Malignancies
• Actual Study Start Date: May 25, 2011
• Actual Primary Completion Date: Sep 15, 2015
• Actual Study Completion Date: Sep 15, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MEDI-551	Drug: MEDI-551; MEDI-551 will be administered by intravenous infusion at dose of 2, 4 or 8 mg/kg once per week on Days 1 and 8 in the first cycle and then once every 28 days at the start of each subsequent cycle

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events [From baseline to 30 days after the last dose of study drug]

Secondary Outcome Measures

1. Number of Participants With Dose Limiting Toxicities [From baseline to 28 days after the first dose of study drug]

   A MEDI-551 treatment-related AE of any toxicity grade that lead to an inability to receive a full cycle (2 doses) of MEDI-551, or, any Grade 3 or higher toxicity that could not be reasonably ascribed to another cause, such as disease progression or accident.

2. Maximum Tolerated Dose [From baseline to 28 days after the first dose of study drug]

   A dose was considered non-tolerated and dose escalation stopped if ≥2 of up to 6 evaluable patients experienced a DLT at any dose level. MTD is the last dose level before the non-tolerated dose.

3. MEDI-551 Trough Concentration Levels at Day 0 (Pre-dose) [Day 0 (pre-dose)]

   Lower limit of quantification for MEDI-551 was 0.1 μg/mL.

4. MEDI-551 Trough Concentration Levels at Day 7 [Day 7]

   Lower limit of quantification for MEDI-551 was 0.1 μg/mL.

5. MEDI-551 Trough Concentration Levels at Day 28 [Day 28]

   Lower limit of quantification for MEDI-551 was 0.1 μg/mL.

6. MEDI-551 Trough Concentration Levels at Day 56 [Day 56]

   Lower limit of quantification for MEDI-551 was 0.1 μg/mL.

7. MEDI-551 Trough Concentration Levels at Day84 [Day 84]

   Lower limit of quantification for MEDI-551 was 0.1 μg/mL.

8. MEDI-551 Trough Concentration Levels at Day 112 [Day 112]

   Lower limit of quantification for MEDI-551 was 0.1 μg/mL.

9. MEDI-551 Trough Concentration Levels at Day 140 [Day 140]

   Lower limit of quantification for MEDI-551 was 0.1 μg/mL.

10. MEDI-551 Trough Concentration Levels at Day 168 [Day 168]

    Lower limit of quantification for MEDI-551 was 0.1 μg/mL.

11. Anti-MEDI-551 Antibodies [From baseline to 30 days after the last dose of study drug]

    Only 1 patient was tested positive for ADA at pre-dose of Cycle 1 Day 1. However, it was considered as false-positive because the titer value was close to the cut point, and this patient was tested negative for ADA at all subsequent cycles post-baseline.

12. Number of Participants With Tumour Response in FL Patients [From the baseline to 30 days after the last dose of study drug]

    Tumour response is defined as complete remission (CR) or partial remission (PR) (Cheson BD et al 2007). CR: Nodal Masses: (a) FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative; (b) Variably FDG-avid or PET negative; regression to normal size on CT; Spleen, Liver: Not palpable, nodules disappeared. Bone Marrow: Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry should be negative. PR: Nodal Masses: ≥50% decrease in sum of the product of the 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; ≥1 PET positive at previously involved site; (b) Variably FDG-avid or PET negative; regression on CT. Spleen, 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; cell type should be specified.

13. Number of Participants With Tumour Response in DLBCL Patients [From the baseline to 30 days after the last dose of study drug]

    Tumour response is defined as complete remission (CR) or partial remission (PR) (Cheson BD et al 2007). CR: Nodal Masses: (a) FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative; (b) Variably FDG-avid or PET negative; regression to normal size on CT; Spleen, Liver: Not palpable, nodules disappeared. Bone Marrow: Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry should be negative. PR: Nodal Masses: ≥50% decrease in sum of the product of the 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; ≥1 PET positive at previously involved site; (b) Variably FDG-avid or PET negative; regression on CT. Spleen, 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; cell type should be specified.

14. Number of Participants With Tumour Response in CLL Patients [From the baseline to 30 days after the last dose of study drug]

    Tumour response is defined as complete remission (CR) or partial remission (PR) (Hallek M et al 2008). CR: all of the following criteria have to be met, and patients have to lack disease-related constitutional symptoms; Lymphadenopathy: None; Hepatomegaly: None; Splenomegaly: None; Blood lymphocytes: <4000/μL; Marrow: Normocellular, <30%lymphocytes, no B-lymphoid nodules, hypocellular marrow defines CR with incomplete marrow recovery; Platelet count: >100000/μL; Hemoglobin: >11.0 g/dL; Neutrophils: >1500/μL PR: at least 2 of the criteria of group A plus 1 of the criteria of group B have to be met. Group A: Lymphadenopathy: Decrease ≥50%; Hepatomegaly: Decrease ≥50%; Splenomegaly: Decrease ≥50%; Blood lymphocytes: Decrease ≥50% from baseline; Marrow: 50% reduction in marrow infiltrate, or B-lymphoid nodules. Group B: Platelet count: 100000/μL or increase ≥50% over baseline; Hemoglobin: >11.0 g/dL or increase ≥50% over baseline; Neutrophils: >1500/μL or >50% improvement over baseline.

15. Number of Participants With Tumour Response in MM Patients [From the baseline to30 days after the last dose of study drug]

    Tumour response is defined as complete response (CR) or partial response (PR) (Durie M et al 2006). CR: Negative immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas and 5% or less plasma cells in bone marrow PR: ≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200mg per 24 h. If the serum and urine M-protein are unmeasurable, a ≥50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. If serum and urine M-protein are unmeasurable, and serum free light assay is also unmeasurable, ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥30%. In addition to the above listed criteria, if present at baseline, a ≥50% reduction in the size of soft tissue plasmacytomas is also required.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 130 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Japanese men or women at least 20 years of age

• Histologically confirmed CLL (excluding small lymphocytic lymphoma (SLL)), DLBCL, FL, or MM.

• Karnofsky Performance Status ≥70;

• Life expectancy of ≥12 weeks

Exclusion Criteria:

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

• Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for treatment of cancer

• Previous therapy directed against CD19, such as monoclonal antibodies or MAb conjugates

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Fukuoka-shi		Japan
2	Research Site	Isehara-shi		Japan
3	Research Site	Nagoya-shi		Japan

Sponsors and Collaborators

• AstraZeneca
• MedImmune LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01957579
• Other Study ID Numbers: D2850C00001; NCT01377116
• First Posted: Oct 8, 2013
• Last Update Posted: Jun 12, 2017
• Last Verified: May 1, 2017

• Keywords provided by AstraZeneca: Phase I; advanced; B cell malignancies; dose escalation; CD19; Japanese
• Additional relevant MeSH terms: Neoplasms; Hematologic Neoplasms

Study Results

Participant Flow

Recruitment Details	First patient enrolled on 25 May 2011. Last patient last visit on 15 September 2015.
Pre-assignment Detail	A total of 32 patients were enrolled into the study. Twelve patients were screen failures, thus 20 patients received MEDI-551.

Arm/Group Title	2 mg/kg	4 mg/kg	8 mg/kg	12 mg/kg
Arm/Group Description	MEDI-551 2 mg/kg	MEDI-551 4 mg/kg	MEDI-551 8 mg/kg	MEDI-551 12 mg/kg
Period Title: Overall Study
STARTED	3	7	4	6
COMPLETED	3	6	2	6
NOT COMPLETED	0	1	2	0

Baseline Characteristics

Arm/Group Title	2 mg/kg	4 mg/kg	8 mg/kg	12 mg/kg	Total
Arm/Group Description	MEDI-551 2mg/kg	MEDI-551 4 mg/kg	MEDI-551 8 mg/kg	MEDI-551 12 mg/kg	Total of all reporting groups
Overall Participants	3	7	4	6	20
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	50.3 (8.1)	57.4 (10.5)	67.0 (8.7)	67.3 (11.4)	61.3 (11.4)
Sex: Female, Male (Count of Participants)
Female	2 66.7%	5 71.4%	0 0%	3 50%	10 50%
Male	1 33.3%	2 28.6%	4 100%	3 50%	10 50%
Disease Type (Number) [Number]
CLL	1 33.3%	0 0%	0 0%	1 16.7%	2 10%
DLBCL	0 0%	2 28.6%	2 50%	2 33.3%	6 30%
FL	2 66.7%	4 57.1%	2 50%	3 50%	11 55%
MM	0 0%	1 14.3%	0 0%	0 0%	1 5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events
Time Frame	From baseline to 30 days after the last dose of study drug

Outcome Measure Data

Analysis Population Description

All patients who received at least 1 dose of MEDI-551.

Arm/Group Title	2 mg/kg	4 mg/kg	8 mg/kg	12 mg/kg
Arm/Group Description	MEDI-551 2 mg/kg	MEDI-551 4 mg/kg	MEDI-551 8 mg/kg	MEDI-551 12 mg/kg
Measure Participants	3	7	4	6
At least 1 Adverse Events (AE)	3 100%	6 85.7%	4 100%	6 100%
At least 1 AE of CTCAE Grade 3 or higher	2 66.7%	2 28.6%	1 25%	3 50%
At least 1 Serious Adverse Events (SAE)	1 33.3%	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Number of Participants With Dose Limiting Toxicities
Description	A MEDI-551 treatment-related AE of any toxicity grade that lead to an inability to receive a full cycle (2 doses) of MEDI-551, or, any Grade 3 or higher toxicity that could not be reasonably ascribed to another cause, such as disease progression or accident.
Time Frame	From baseline to 28 days after the first dose of study drug

Outcome Measure Data

Analysis Population Description

All subjects in the dose escalation phase who have received MEDI-551 at Day 1 and Day 8 and completed the safety follow-up through the dose-limiting toxicity (DLT) evaluation period (28 days), or who experienced a DLT.

Arm/Group Title	2 mg/kg	4 mg/kg	8 mg/kg	12 mg/kg
Arm/Group Description	MEDI-551 2 mg/kg	MEDI-551 4 mg/kg	MEDI-551 8 mg/kg	MEDI-551 12 mg/kg
Measure Participants	3	6	3	6
At least 1 Dose Limiting Toxicity	0 0%	1 14.3%	0 0%	2 33.3%
CTCAE Grade 3 or higher non-hematologic toxicity	0 0%	1 14.3%	0 0%	1 16.7%
CTCAE Grade 3 or higher hematologic toxicity	0 0%	0 0%	0 0%	1 16.7%

3. Secondary Outcome

Title	Maximum Tolerated Dose
Description	A dose was considered non-tolerated and dose escalation stopped if ≥2 of up to 6 evaluable patients experienced a DLT at any dose level. MTD is the last dose level before the non-tolerated dose.
Time Frame	From baseline to 28 days after the first dose of study drug

Outcome Measure Data

Analysis Population Description

All subjects in the dose escalation phase who have received MEDI-551 at Day 1 and Day 8 and completed the safety follow-up through the dose-limiting toxicity (DLT) evaluation period (28 days), or who experienced a DLT.

Arm/Group Title	MEDI-551
Arm/Group Description	MEDI-551 2, 4, 8 and 12 mg/kg were evaluated
Measure Participants	18
Number [mg/kg]	8

4. Secondary Outcome

Title	MEDI-551 Trough Concentration Levels at Day 0 (Pre-dose)
Description	Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time Frame	Day 0 (pre-dose)

Outcome Measure Data

Analysis Population Description

Patients who have trough concentration data at Day 0 (pre-dose)

Arm/Group Title	2 mg/kg	4 mg/kg	8 mg/kg	12 mg/kg
Arm/Group Description	MEDI-551 2 mg/kg	MEDI-551 4 mg/kg	MEDI-551 8 mg/kg	MEDI-551 12 mg/kg
Measure Participants	3	7	4	6
Mean (Standard Deviation) [μg/mL]	NA (NA)	NA (NA)	NA (NA)	NA (NA)

5. Secondary Outcome

Title	MEDI-551 Trough Concentration Levels at Day 7
Description	Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

Patients who have trough concentration data at Day 7

Arm/Group Title	2 mg/kg	4 mg/kg	8 mg/kg	12 mg/kg
Arm/Group Description	MEDI-551 2 mg/kg	MEDI-551 4 mg/kg	MEDI-551 8 mg/kg	MEDI-551 12 mg/kg
Measure Participants	3	6	4	4
Mean (Standard Deviation) [μg/mL]	21.3 (8.65)	39.2 (9.13)	91.9 (31.1)	104 (29.0)

6. Secondary Outcome

Title	MEDI-551 Trough Concentration Levels at Day 28
Description	Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

Patients who have trough concentration data at Day 28

Arm/Group Title	2 mg/kg	4 mg/kg	8 mg/kg	12 mg/kg
Arm/Group Description	MEDI-551 2 mg/kg	MEDI-551 4 mg/kg	MEDI-551 8 mg/kg	MEDI-551 12 mg/kg
Measure Participants	3	5	3	4
Mean (Standard Deviation) [μg/mL]	23.2 (5.82)	36.2 (5.34)	103 (29.0)	115 (21.3)

7. Secondary Outcome

Title	MEDI-551 Trough Concentration Levels at Day 56
Description	Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time Frame	Day 56

Outcome Measure Data

Analysis Population Description

Patients who have trough concentration data at Day 56

Arm/Group Title	2 mg/kg	4 mg/kg	8 mg/kg	12 mg/kg
Arm/Group Description	MEDI-551 2 mg/kg	MEDI-551 4 mg/kg	MEDI-551 8 mg/kg	MEDI-551 12 mg/kg
Measure Participants	3	5	3	4
Mean (Standard Deviation) [μg/mL]	22.0 (4.92)	33.2 (6.92)	89.5 (13.9)	114 (33.1)

8. Secondary Outcome

Title	MEDI-551 Trough Concentration Levels at Day84
Description	Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time Frame	Day 84

Outcome Measure Data

Analysis Population Description

Patients who have trough concentration data at Day 84

Arm/Group Title	2 mg/kg	4 mg/kg	8 mg/kg	12 mg/kg
Arm/Group Description	MEDI-551 2 mg/kg	MEDI-551 4 mg/kg	MEDI-551 8 mg/kg	MEDI-551 12 mg/kg
Measure Participants	3	4	3	4
Mean (Standard Deviation) [μg/mL]	21.7 (4.40)	33.7 (4.24)	91.6 (9.25)	103 (26.3)

9. Secondary Outcome

Title	MEDI-551 Trough Concentration Levels at Day 112
Description	Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time Frame	Day 112

Outcome Measure Data

Analysis Population Description

Patients who have trough concentration data at Day 112

Arm/Group Title	2 mg/kg	4 mg/kg	8 mg/kg	12 mg/kg
Arm/Group Description	MEDI-551 2 mg/kg	MEDI-551 4 mg/kg	MEDI-551 8 mg/kg	MEDI-551 12 mg/kg
Measure Participants	3	4	2	4
Mean (Standard Deviation) [μg/mL]	22.9 (3.10)	35.3 (5.07)	85.5 (NA)	114 (64.4)

10. Secondary Outcome

Title	MEDI-551 Trough Concentration Levels at Day 140
Description	Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time Frame	Day 140

Outcome Measure Data

Analysis Population Description

Patients who have trough concentration data at Day 140

Arm/Group Title	2 mg/kg	4 mg/kg	8 mg/kg	12 mg/kg
Arm/Group Description	MEDI-551 2 mg/kg	MEDI-551 4 mg/kg	MEDI-551 8 mg/kg	MEDI-551 12 mg/kg
Measure Participants	2	4	2	4
Mean (Standard Deviation) [μg/mL]	22.1 (NA)	36.3 (10.5)	86.1 (NA)	117 (62.0)

11. Secondary Outcome

Title	MEDI-551 Trough Concentration Levels at Day 168
Description	Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time Frame	Day 168

Outcome Measure Data

Analysis Population Description

Patients who have trough concentration data at Day 168

Arm/Group Title	2 mg/kg	4 mg/kg	8 mg/kg	12 mg/kg
Arm/Group Description	MEDI-551 2 mg/kg	MEDI-551 4 mg/kg	MEDI-551 8 mg/kg	MEDI-551 12 mg/kg
Measure Participants	2	3	2	2
Mean (Standard Deviation) [μg/mL]	20.0 (NA)	31.4 (8.30)	94.1 (NA)	82.1 (NA)

12. Secondary Outcome

Title	Anti-MEDI-551 Antibodies
Description	Only 1 patient was tested positive for ADA at pre-dose of Cycle 1 Day 1. However, it was considered as false-positive because the titer value was close to the cut point, and this patient was tested negative for ADA at all subsequent cycles post-baseline.
Time Frame	From baseline to 30 days after the last dose of study drug

Outcome Measure Data

Analysis Population Description

Patients who have at least one post-baseline sample for Anti-MEDI-551 antibodies.

Arm/Group Title	2 mg/kg	4 mg/kg	8 mg/kg	12 mg/kg
Arm/Group Description	MEDI-551 2 mg/kg	MEDI-551 4 mg/kg	MEDI-551 8 mg/kg	MEDI-551 12 mg/kg
Measure Participants	3	7	4	6
positive at least 1 time point	0 0%	0 0%	1 25%	0 0%
negative at all time points	3 100%	7 100%	3 75%	6 100%

13. Secondary Outcome

Title	Number of Participants With Tumour Response in FL Patients
Description	Tumour response is defined as complete remission (CR) or partial remission (PR) (Cheson BD et al 2007). CR: Nodal Masses: (a) FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative; (b) Variably FDG-avid or PET negative; regression to normal size on CT; Spleen, Liver: Not palpable, nodules disappeared. Bone Marrow: Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry should be negative. PR: Nodal Masses: ≥50% decrease in sum of the product of the 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; ≥1 PET positive at previously involved site; (b) Variably FDG-avid or PET negative; regression on CT. Spleen, 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; cell type should be specified.
Time Frame	From the baseline to 30 days after the last dose of study drug

Outcome Measure Data

Analysis Population Description

All patients with FL who received at least 1 dose of MEDI-551 and completed at least 1 post-baseline disease assessment.

Arm/Group Title	2 mg/kg (FL)	4 mg/kg (FL)	8 mg/kg (FL)	12 mg/kg (FL)
Arm/Group Description	FL patients in MEDI-551 2 mg/kg cohort	FL patients in MEDI-551 4 mg/kg cohort	FL patients in MEDI-551 8 mg/kg cohort	FL patients in MEDI-551 12 mg/kg cohort
Measure Participants	2	4	2	3
Number [Participants]	2 66.7%	3 42.9%	2 50%	2 33.3%

14. Secondary Outcome

Title	Number of Participants With Tumour Response in DLBCL Patients
Description	Tumour response is defined as complete remission (CR) or partial remission (PR) (Cheson BD et al 2007). CR: Nodal Masses: (a) FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative; (b) Variably FDG-avid or PET negative; regression to normal size on CT; Spleen, Liver: Not palpable, nodules disappeared. Bone Marrow: Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry should be negative. PR: Nodal Masses: ≥50% decrease in sum of the product of the 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; ≥1 PET positive at previously involved site; (b) Variably FDG-avid or PET negative; regression on CT. Spleen, 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; cell type should be specified.
Time Frame	From the baseline to 30 days after the last dose of study drug

Outcome Measure Data

Analysis Population Description

All patients with DLBCL who received at least 1 dose of MEDI-551 and completed at least 1 post-baseline disease assessment.

Arm/Group Title	2 mg/kg (DLBCL)	4 mg/kg (DLBCL)	8 mg/kg (DLBCL)	12 mg/kg (DLBCL)
Arm/Group Description	DLBCL patients in MEDI-551 2 mg/kg cohort	DLBCL patients in MEDI-551 4 mg/kg cohort	DLBCL patients in MEDI-551 8 mg/kg cohort	DLBCL patients in MEDI-551 12 mg/kg cohort
Measure Participants	0	2	2	2
Number [Participants]	0 0%	1 14.3%	2 50%

15. Secondary Outcome

Title	Number of Participants With Tumour Response in CLL Patients
Description	Tumour response is defined as complete remission (CR) or partial remission (PR) (Hallek M et al 2008). CR: all of the following criteria have to be met, and patients have to lack disease-related constitutional symptoms; Lymphadenopathy: None; Hepatomegaly: None; Splenomegaly: None; Blood lymphocytes: <4000/μL; Marrow: Normocellular, <30%lymphocytes, no B-lymphoid nodules, hypocellular marrow defines CR with incomplete marrow recovery; Platelet count: >100000/μL; Hemoglobin: >11.0 g/dL; Neutrophils: >1500/μL PR: at least 2 of the criteria of group A plus 1 of the criteria of group B have to be met. Group A: Lymphadenopathy: Decrease ≥50%; Hepatomegaly: Decrease ≥50%; Splenomegaly: Decrease ≥50%; Blood lymphocytes: Decrease ≥50% from baseline; Marrow: 50% reduction in marrow infiltrate, or B-lymphoid nodules. Group B: Platelet count: 100000/μL or increase ≥50% over baseline; Hemoglobin: >11.0 g/dL or increase ≥50% over baseline; Neutrophils: >1500/μL or >50% improvement over baseline.
Time Frame	From the baseline to 30 days after the last dose of study drug

Outcome Measure Data

Analysis Population Description

All patients with CLL who received at least 1 dose of MEDI-551 and completed at least 1 post-baseline disease assessment.

Arm/Group Title	2 mg/kg (CLL)	4 mg/kg (CLL)	8 mg/kg (CLL)	12 mg/kg (CLL)
Arm/Group Description	CLL patients in MEDI-551 2 mg/kg cohort	CLL patients in MEDI-551 4 mg/kg cohort	CLL patients in MEDI-551 8 mg/kg cohort	CLL patients in MEDI-551 12 mg/kg cohort
Measure Participants	1	0	0	1
Number [Participants]	1 33.3%	0 0%

16. Secondary Outcome

Title	Number of Participants With Tumour Response in MM Patients
Description	Tumour response is defined as complete response (CR) or partial response (PR) (Durie M et al 2006). CR: Negative immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas and 5% or less plasma cells in bone marrow PR: ≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200mg per 24 h. If the serum and urine M-protein are unmeasurable, a ≥50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. If serum and urine M-protein are unmeasurable, and serum free light assay is also unmeasurable, ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥30%. In addition to the above listed criteria, if present at baseline, a ≥50% reduction in the size of soft tissue plasmacytomas is also required.
Time Frame	From the baseline to30 days after the last dose of study drug

Outcome Measure Data

Analysis Population Description

All patients with MM who received at least 1 dose of MEDI-551 and completed at least 1 post-baseline disease assessment.

Arm/Group Title	2 mg/kg (MM)	4 mg/kg (MM)	8 mg/kg (MM)	12 mg/kg (MM)
Arm/Group Description	MM patients in MEDI-551 2 mg/kg cohort	MM patients in MEDI-551 4 mg/kg cohort	MM patients in MEDI-551 8 mg/kg cohort	MM patients in MEDI-551 12 mg/kg cohort
Measure Participants	0	1	0	0
Number [Participants]	0 0%

Adverse Events

Time Frame	AEs were collected throughout the study, from informed consent until the end of 30 days after study treatment. The follow-up period is defined as 3 months after study treatment is discontinued.
Arm/Group Title	2 mg/kg		4 mg/kg		8 mg/kg		12 mg/kg
Arm/Group Description	MEDI-551 2mg/kg		MEDI-551 4 mg/kg		MEDI-551 8 mg/kg		MEDI-551 12 mg/kg
All Cause Mortality
	2 mg/kg		4 mg/kg		8 mg/kg		12 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	2 mg/kg		4 mg/kg		8 mg/kg		12 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		0/7 (0%)		0/4 (0%)		0/6 (0%)
Infections and infestations
Epiglottitis	1/3 (33.3%)		0/7 (0%)		0/4 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	2 mg/kg		4 mg/kg		8 mg/kg		12 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		6/7 (85.7%)		4/4 (100%)		6/6 (100%)
Blood and lymphatic system disorders
Leukopenia	0/3 (0%)		1/7 (14.3%)		1/4 (25%)		1/6 (16.7%)
Neutropenia	0/3 (0%)		1/7 (14.3%)		0/4 (0%)		1/6 (16.7%)
Febrile neutropenia	0/3 (0%)		0/7 (0%)		1/4 (25%)		0/6 (0%)
Lymphadenitis	1/3 (33.3%)		0/7 (0%)		0/4 (0%)		0/6 (0%)
Eye disorders
Conjunctivitis allergic	0/3 (0%)		0/7 (0%)		0/4 (0%)		1/6 (16.7%)
Eyelid oedema	0/3 (0%)		1/7 (14.3%)		0/4 (0%)		0/6 (0%)
Gastrointestinal disorders
Constipation	0/3 (0%)		1/7 (14.3%)		0/4 (0%)		1/6 (16.7%)
Abdominal pain upper	0/3 (0%)		0/7 (0%)		1/4 (25%)		0/6 (0%)
Diarrhoea	0/3 (0%)		0/7 (0%)		0/4 (0%)		1/6 (16.7%)
Dry mouth	0/3 (0%)		0/7 (0%)		1/4 (25%)		0/6 (0%)
Proctalgia	0/3 (0%)		0/7 (0%)		1/4 (25%)		0/6 (0%)
Stomatitis	0/3 (0%)		1/7 (14.3%)		0/4 (0%)		0/6 (0%)
General disorders
Fatigue	1/3 (33.3%)		1/7 (14.3%)		0/4 (0%)		0/6 (0%)
Influenza like illness	1/3 (33.3%)		1/7 (14.3%)		0/4 (0%)		0/6 (0%)
Pyrexia	0/3 (0%)		1/7 (14.3%)		0/4 (0%)		0/6 (0%)
Hepatobiliary disorders
Hepatic function abnormal	0/3 (0%)		0/7 (0%)		0/4 (0%)		1/6 (16.7%)
Infections and infestations
Nasopharyngitis	1/3 (33.3%)		0/7 (0%)		1/4 (25%)		1/6 (16.7%)
Upper respiratory tract infection	1/3 (33.3%)		0/7 (0%)		0/4 (0%)		1/6 (16.7%)
Bronchitis	0/3 (0%)		0/7 (0%)		0/4 (0%)		1/6 (16.7%)
Oral candidiasis	0/3 (0%)		1/7 (14.3%)		0/4 (0%)		0/6 (0%)
Injury, poisoning and procedural complications
Infusion related reaction	2/3 (66.7%)		1/7 (14.3%)		3/4 (75%)		3/6 (50%)
Investigations
White blood cell count decreased	2/3 (66.7%)		2/7 (28.6%)		0/4 (0%)		0/6 (0%)
Lymphocyte count decreased	1/3 (33.3%)		2/7 (28.6%)		0/4 (0%)		0/6 (0%)
Neutrophil count decreased	1/3 (33.3%)		2/7 (28.6%)		0/4 (0%)		0/6 (0%)
Platelet count decreased	0/3 (0%)		1/7 (14.3%)		1/4 (25%)		0/6 (0%)
Aspartate aminotransferase increased	1/3 (33.3%)		0/7 (0%)		0/4 (0%)		0/6 (0%)
Blood cholesterol increased	0/3 (0%)		0/7 (0%)		1/4 (25%)		0/6 (0%)
Blood creatine phosphokinase increased	0/3 (0%)		0/7 (0%)		0/4 (0%)		1/6 (16.7%)
Blood creatinine increased	0/3 (0%)		0/7 (0%)		1/4 (25%)		0/6 (0%)
Blood lactate dehydrogenase increased	1/3 (33.3%)		0/7 (0%)		0/4 (0%)		0/6 (0%)
Blood triglycerides increased	1/3 (33.3%)		0/7 (0%)		0/4 (0%)		0/6 (0%)
Metabolism and nutrition disorders
Hypertriglyceridaemia	1/3 (33.3%)		1/7 (14.3%)		4/4 (100%)		0/6 (0%)
Musculoskeletal and connective tissue disorders
Monarthritis	0/3 (0%)		1/7 (14.3%)		0/4 (0%)		0/6 (0%)
Myalgia	0/3 (0%)		1/7 (14.3%)		0/4 (0%)		0/6 (0%)
Spinal osteoarthritis	0/3 (0%)		1/7 (14.3%)		0/4 (0%)		0/6 (0%)
Musculoskeletal chest pain	0/3 (0%)		1/7 (14.3%)		0/4 (0%)		0/6 (0%)
Musculoskeletal stiffness	0/3 (0%)		0/7 (0%)		1/4 (25%)		0/6 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cholesteatoma	0/3 (0%)		0/7 (0%)		0/4 (0%)		1/6 (16.7%)
Sebaceous adenoma	0/3 (0%)		0/7 (0%)		0/4 (0%)		1/6 (16.7%)
Nervous system disorders
Headache	0/3 (0%)		1/7 (14.3%)		0/4 (0%)		0/6 (0%)
Peripheral sensory neuropathy	0/3 (0%)		0/7 (0%)		1/4 (25%)		0/6 (0%)
Psychiatric disorders
Insomnia	0/3 (0%)		1/7 (14.3%)		0/4 (0%)		1/6 (16.7%)
Renal and urinary disorders
Calculus ureteric	1/3 (33.3%)		0/7 (0%)		0/4 (0%)		0/6 (0%)
Haematuria	1/3 (33.3%)		0/7 (0%)		0/4 (0%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/3 (0%)		1/7 (14.3%)		0/4 (0%)		0/6 (0%)
Upper respiratory tract inflammation	0/3 (0%)		0/7 (0%)		0/4 (0%)		1/6 (16.7%)
Skin and subcutaneous tissue disorders
Rash	1/3 (33.3%)		2/7 (28.6%)		0/4 (0%)		0/6 (0%)
Drug eruption	0/3 (0%)		0/7 (0%)		1/4 (25%)		0/6 (0%)
Eczema	0/3 (0%)		1/7 (14.3%)		0/4 (0%)		0/6 (0%)
Vascular disorders
Hypertension	0/3 (0%)		2/7 (28.6%)		0/4 (0%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.