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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Blood Cancer, Advanced B Cell Malignancies

Intervention / Treatment
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* Drug: MEDI-551


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI-551<br> | Drug: MEDI-551<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events |  | From baseline to 30 days after the last dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicities | 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. | From baseline to 28 days after the first dose of study drug | 
| Maximum Tolerated Dose | 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. | From baseline to 28 days after the first dose of study drug | 
| MEDI-551 Trough Concentration Levels at Day 0 (Pre-dose) | Lower limit of quantification for MEDI-551 was 0.1 μg/mL. | Day 0 (pre-dose) | 
| MEDI-551 Trough Concentration Levels at Day 7 | Lower limit of quantification for MEDI-551 was 0.1 μg/mL. | Day 7 | 
| MEDI-551 Trough Concentration Levels at Day 28 | Lower limit of quantification for MEDI-551 was 0.1 μg/mL. | Day 28 | 
| MEDI-551 Trough Concentration Levels at Day 56 | Lower limit of quantification for MEDI-551 was 0.1 μg/mL. | Day 56 | 
| MEDI-551 Trough Concentration Levels at Day84 | Lower limit of quantification for MEDI-551 was 0.1 μg/mL. | Day 84 | 
| MEDI-551 Trough Concentration Levels at Day 112 | Lower limit of quantification for MEDI-551 was 0.1 μg/mL. | Day 112 | 
| MEDI-551 Trough Concentration Levels at Day 140 | Lower limit of quantification for MEDI-551 was 0.1 μg/mL. | Day 140 | 
| MEDI-551 Trough Concentration Levels at Day 168 | Lower limit of quantification for MEDI-551 was 0.1 μg/mL. | Day 168 | 
| Anti-MEDI-551 Antibodies | 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. | From baseline to 30 days after the last dose of study drug | 
| Number of Participants With Tumour Response in FL Patients | 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. | From the baseline to 30 days after the last dose of study drug | 
| Number of Participants With Tumour Response in DLBCL Patients | 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. | From the baseline to 30 days after the last dose of study drug | 
| Number of Participants With Tumour Response in CLL Patients | 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. | From the baseline to 30 days after the last dose of study drug | 
| Number of Participants With Tumour Response in MM Patients | 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. | From the baseline to30 days after the last dose of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, advanced, B cell malignancies, dose escalation, CD19, Japanese