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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
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
Research Site
Fukuoka, Japan
Research Site
Isehara-shi, Japan
Research Site
Nagoya, Japan
Number of Participants With Adverse Events
Time frame: From baseline to 30 days after the last dose of study drug
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.
Time frame: 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.
Time frame: 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.
Time frame: Day 0 (pre-dose)
MEDI-551 Trough Concentration Levels at Day 7
Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time frame: Day 7
MEDI-551 Trough Concentration Levels at Day 28
Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time frame: Day 28
MEDI-551 Trough Concentration Levels at Day 56
Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time frame: Day 56
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MEDI-551 Trough Concentration Levels at Day84
Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time frame: Day 84
MEDI-551 Trough Concentration Levels at Day 112
Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time frame: Day 112
MEDI-551 Trough Concentration Levels at Day 140
Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time frame: Day 140
MEDI-551 Trough Concentration Levels at Day 168
Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From the baseline to30 days after the last dose of study drug