Anti-CXCR4 (BMS-936564) Alone and in Combination With Lenalidomide/Dexamethasone or Bortezomib/Dexamethasone in Relapsed/Refractory Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to determine 1) the safety and tolerability of multiple intravenous doses of anti-CXCR4 (BMS-936564) as monotherapy and as combination, and 2) the maximum tolerated dose (MTD) of BMS-936564 in combination with Lenalidomide/Dexamethasone or Bortezomib/Dexamethasone in subjects with relapsed or refractory multiple myeloma.

Official Title
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A Phase 1b, Open-label, Multicenter Study of (BMS-936564) in Combination With Lenalidomide (Revlimid) Plus Low-dose Dexamethasone, or With Bortezomib (Velcade) Plus Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: Anti-CXCR4 (BMS-936564)
* Biological: Lenalidomide
* Biological: Dexamethasone
* Biological: Anti-CXCR4 (BMS-936564)
* Biological: Bortezomib
* Biological: Dexamethasone


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: Subjects must have confirmed diagnosis of multiple myeloma with measurable disease Excluded are subjects with only plasmacytomas, plasma cell leukemia, or non-secretory myeloma. Disease must be assessed within 28 days prior to treatment initiation. Subjects must have evidence of relapsed or relapsed/refractory disease. Subjects must have received at least 2 prior regimens for multiple myeloma. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2. Subjects must have received last treatment (ie, chemotherapy, radiotherapy, biological, immunotherapy or investigational agent [therapeutic or diagnostic]) at least 14 days prior to treatment initiation. The last treatment of systemically absorbed steroids must be at least 2 weeks or 5 half lives (whichever is shorter) before the first dose of BMS-936564. Exclusion Criteria: A serious uncontrolled medical disorder or active infection. Current or recent (within 3 months) gastrointestinal disease or condition that could impact the absorption of orally-administered drug. Inability to swallow oral medication. Uncontrolled or significant heart disease. Any other malignancy, excluding basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, localized prostate cancer, or superficial bladder cancer stage 0, from which the subject has not been disease-free for at least 3 years.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Anti-CXCR4 (BMS-936564)+Lenalidomide+Dexamethasone<br> | Biological: Anti-CXCR4 (BMS-936564)<br>* Solution, Intravenously, 1-10 mg/kg, Single 60 minute infusion once a week, 42 days (cycle 1) 28 days subsequent cycles<br>* Other names: Anti-CXCR4;Biological: Lenalidomide<br>* Tablets, per os (by mouth route of administration) (P.O), 25 mg, daily for 21 days (Day 15-35 in cycle 1; Day 1-21 in subsequent cycles), no dosing in Cycle 1, Cycle 2 +:daily dosing from Day 1-21<br>* Other names: Revlimid®;Biological: Dexamethasone<br>* Tablets, per os (by mouth route of administration) (P.O), 40 mg, administered with Lenalidomide once every 7 days, 42 days (cycle 1) 28 days subsequent cycles<br>|
| Experimental: Arm B: Anti-CXCR4 (BMS-936564)+Bortezomib+Dexamethasone<br> | Biological: Anti-CXCR4 (BMS-936564)<br>* Solution, Intravenously, 1-10 mg/kg, Single 60 minute infusion once a week, 35 days (cycle 1) 21 days subsequent cycles<br>* Other names: Anti-CXCR4;Biological: Bortezomib<br>* Intravenous (IV), 1.3 mg/m2, administered on day 15, 18, 22, 25 in cycle 1, then on Day 1, 4, 8, 11 in subsequent cycles, no dosing in Cycle 1, Cycle 2 +:dosing on Day 1, 4, 8, 11<br>* Other names: Velcade®;Biological: Dexamethasone<br>* Tablets, per os (by mouth route of administration) (P.O), 40 mg, administered on the day of (and the day after) Bortezomib infusion, 35 days (cycle 1) 21 days subsequent cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of maximum tolerated dose |  | 42 days in Arm A | 
| Determination of maximum tolerated dose |  | 35 days in Arm B | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability will be analyzed for all patients. Safety endpoints will be based on adverse event reports, and include frequent adverse event (AE)s, serious adverse event (SAE)s and lab abnormalities | Additionally safety will be measures using vital signs, electrocardiogram (ECG)s, Multiple gated acquisition scan (MUGA) or echocardiograms (ECHO), physical examination, radiology exams, skeletal survey and clinical laboratory tests | Safety will be evaluated up to 2 years | 
| Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be maximum observed concentration (Cmax) |  | PK samples will be collected multiple time points during Cycle 1 (Arm A is Day 1-42, Arm B is Day 1-35). In Cycle 2 samples will be collected on days 1, 8 & 15, at end of treatment & during the follow-up visit. Similar PK sampling will occur in Arm A & B | 
| Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be trough observed concentration (Cmin) |  | PK samples will be collected multiple time points during Cycle 1 (Arm A is Day 1-42, Arm B is Day 1-35). In Cycle 2 samples will be collected on days 1, 8 & 15, at end of treatment & during the follow-up visit. Similar PK sampling will occur in Arm A & B | 
| Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be time of maximum observed concentration (Tmax) |  | PK samples will be collected multiple time points during Cycle 1 (Arm A is Day 1-42, Arm B is Day 1-35). In Cycle 2 samples will be collected on days 1, 8 & 15, at end of treatment & during the follow-up visit. Similar PK sampling will occur in Arm A & B | 
| Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be area under the concentration-time curve in one dosing interval (AUC (TAU)) |  | PK samples will be collected multiple time points during Cycle 1 (Arm A is Day 1-42, Arm B is Day 1-35). In Cycle 2 samples will be collected on days 1, 8 & 15, at end of treatment & during the follow-up visit. Similar PK sampling will occur in Arm A & B | 
| Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be half-life (T-Half) |  | PK samples will be collected multiple time points during Cycle 1 (Arm A is Day 1-42, Arm B is Day 1-35). In Cycle 2 samples will be collected on days 1, 8 & 15, at end of treatment & during the follow-up visit. Similar PK sampling will occur in Arm A & B | 
| Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) |  | PK samples will be collected multiple time points during Cycle 1 (Arm A is Day 1-42, Arm B is Day 1-35). In Cycle 2 samples will be collected on days 1, 8 & 15, at end of treatment & during the follow-up visit. Similar PK sampling will occur in Arm A & B | 
| Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be total body clearance (CLT) |  | PK samples will be collected multiple time points during Cycle 1 (Arm A is Day 1-42, Arm B is Day 1-35). In Cycle 2 samples will be collected on days 1, 8 & 15, at end of treatment & during the follow-up visit. Similar PK sampling will occur in Arm A & B | 
| Pharmacokinetic (PK) measures will be collected for all patients who received study medication. The pharmacokinetic parameters will be volume of distribution at steady-state (Vss) |  | PK samples will be collected multiple time points during Cycle 1 (Arm A is Day 1-42, Arm B is Day 1-35). In Cycle 2 samples will be collected on days 1, 8 & 15, at end of treatment & during the follow-up visit. Similar PK sampling will occur in Arm A & B | 
| Individual tumor responses as defined by the International Myeloma Working Group Uniform Response Criteria (IMWG) for Multiple Myeloma (MM) will be used to monitor efficacy. For this assessment blood urine, and/or bone marrow assessment will be used |  | within 28 days prior to first dose | 
| Anti-tumor response will be assessed by IMWG criteria (blood and urine; Bone marrow will not be collected unless to confirm complete response (CR)) |  | On Cycle 1 day 14 | 
| Anti-tumor response will be assessed by IMWG criteria (blood and urine; Bone marrow assessment will be collected during screening period, at end of cycle 1, end of cycle 4 and to confirm CR ) |  | At end of each Cycle | 
| Samples will be collected to characterize immunogenicity |  | For Arm A, blood samples will be collected prior to dosing administration on Cycle 1 (predose & Days 1, 15, & 29), Cycle 2 Day 1, Cycle 3 Day 1; & Day 1 of Cycle 6 & every 6 cycles, end of treatment, & at 3 & 6 month follow-up visits, if available | 
| Samples will be collected to characterize immunogenicity |  | For Arm B, blood samples will be collected at Cycle 1 (predose & Days 1, 15, & 29), Cycle 2 Day 1, Cycle 3 Day 1; Cycle 4 Day 1; & Day 1 on Cycle 8 & every 8 cycles, if available, end of treatment, & at 3 & 6 month follow-up visits, if available | 
| Baseline level of cytokines/chemokines/growth factors will be determined, but not limited to SDF1 in peripheral blood and bone marrow |  | Sample will be collected within 28 days prior to first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed, Refractory