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The purpose of this study is to determine the side effects of treatment with the monoclonal antibody anti-PD-L1 (BMS-936559) in subjects with compromised bone marrow function and the dose that should be recommended for use in future studies.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: BMS-936559 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BMS-936559 (Anti PD-L1) | Biological | Injection for infusion, Intravenous (IV), 1, 3 or 10 mg/kg, Every 2 weeks, 48-96 weeks depending on response |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability of BMS-936559 as measured by the incidence of adverse events (AEs), serious AEs, dose-limiting toxicities, laboratory test abnormalities, and changes in vital signs | Weeks 1 | |
| Safety and tolerability of BMS-936559 as measured by the incidence of adverse events (AEs), serious AEs, dose-limiting toxicities, laboratory test abnormalities, and changes in vital signs | Weeks 2 | |
| Safety and tolerability of BMS-936559 as measured by the incidence of adverse events (AEs), serious AEs, dose-limiting toxicities, laboratory test abnormalities, and changes in vital signs | Weeks 3 | |
| Safety and tolerability of BMS-936559 as measured by the incidence of adverse events (AEs), serious AEs, dose-limiting toxicities, laboratory test abnormalities, and changes in vital signs | Weeks 6 | |
| Safety and tolerability of BMS-936559 as measured by the incidence of adverse events (AEs), serious AEs, dose-limiting toxicities, laboratory test abnormalities, and changes in vital signs | Every 2 weeks until 70 days after last treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics of BMS-936559 as measured by maximum observed serum concentration (Cmax) | Within the first 22 weeks, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment) | |
| Pharmacokinetics of BMS-936559 as measured by time of maximum observed serum concentration (Tmax) |
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Inclusion Criteria:
Eastern Cooperative Oncology Group (ECOG) Performance of 0 or 1
Subjects must have histological confirmation of relapsed or refractory hematologic malignancy
Subjects with non-Hodgkin's lymphoma or Hodgkin lymphoma must have at least one measureable lesion as defined by lymphoma response criteria. Tumor sites that are considered measureable must not have received prior radiation therapy
Subjects with multiple myeloma (MM) must have detectable disease as measured by presence of monoclonal immunoglobulin protein in a serum electrophoresis: IgG, IgA, IgM, (M-protein ≥ 0.5 g/dl or serum IgD M-protein ≥ 0.05 g/dl) or serum free-light chain or 24 hour urine with free light chain. Excluded are subjects with only plasmacytomas, plasma cell leukemia, or non-secretory myeloma
Subjects with chronic myelogenous leukemia (CML) must have evidence of the Philadelphia chromosome by polymerase chain reaction (PCR) or chromosome analysis
Life expectancy of at least 3 months
For subjects with lymphoma, either a formalin fixed tissue block or 7 to 15 slides of tumor sample (archival or fresh) must be available for performance of correlative studies
Subjects must have received at least one prior chemotherapy regimen. Subjects must be off therapy for at least 4 weeks ( 2 weeks for oral agents) prior to Day 1
Prior palliative radiation must have been completed at least 2 weeks prior to study Day 1
Toxicities related to prior therapy must have returned to Grade 1 or less, except for alopecia. Peripheral neuropathy must be Grade 2 or less
Adequate bone marrow function defined as:
Adequate renal parameters defined as Creatinine clearance (CrCl) > 40 ml/min (Cockcroft-Gault formula)
Adequate hepatic parameters defined as:
Women of child bearing potential (WOCBP) and for at least 70 days after the last dose of investigational product
Men and women ≥ 18 years of age
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
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| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D006689 | Hodgkin Disease |
| D009101 | Multiple Myeloma |
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
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| ID | Term |
|---|---|
| C000627113 | BMS-936559 |
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| Within the first 22 weeks, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment) |
| Pharmacokinetics of BMS-936559 as measured by area under the serum concentration time curve in the dosing interval [AUC(TAU)] | Within the first 22 weeks, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment) |
| Pharmacokinetics of BMS-936559 as measured by accumulation index (AI) calculated ar ratio of the AUC(TAU) at steady state and first dose | Within the first 22 weeks, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment) |
| Pharmacokinetics of BMS-936559 as measured by serum concentration achieved at the end of dosing interval (trough concentration) (Cmin) | Within the first 22 weeks, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment) |
| Pharmacokinetics of BMS-936559 as measured by serum concentration achieved at the end of the infusion (Ceoinf) | Within the first 22 weeks, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment) |
| Antitumor activity of BMS-936559 as measured by the objective response rate, duration of response, and progression free survival | Week 4, week 12, week 20, and every 16 weeks until confirmed disease progression assessed up to Week 214 |
| Immunogenicity of BMS-936559 as measured by the frequency of subjects with an increase in anti-drug antibody levels from baseline | Baseline, weeks 3, weeks 12, weeks 20, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment) |
| Programmed death ligand 1 (PD-L1) receptor occupancy levels as measured by changes from baseline | Baseline and within the first 3 weeks |
| D008206 |
| Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D054219 | Neoplasms, Plasma Cell |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006474 | Hemorrhagic Disorders |
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |