A Phase 1, Dose-escalation Study of MEDI-551 in Japanese Adult Patients With Relapsed or Refractory Advanced B-cell Malignancies
- Registration Number
- NCT01957579
- Lead Sponsor
- AstraZeneca
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description MEDI-551 MEDI-551 -
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events From baseline to 30 days after the last dose of study drug
- Secondary Outcome Measures
Name Time Method MEDI-551 Trough Concentration Levels at Day 28 Day 28 Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
MEDI-551 Trough Concentration Levels at Day 140 Day 140 Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
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.MEDI-551 Trough Concentration Levels at Day 112 Day 112 Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
MEDI-551 Trough Concentration Levels at Day 56 Day 56 Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
MEDI-551 Trough Concentration Levels at Day 168 Day 168 Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
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.
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.MEDI-551 Trough Concentration Levels at Day84 Day 84 Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
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.
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.
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.
MEDI-551 Trough Concentration Levels at Day 7 Day 7 Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
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.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.
Trial Locations
- Locations (1)
Research Site
🇯🇵Nagoya-shi, Japan