Multiple Ascending Dose (MAD) Combination in Subjects With Multiple Myeloma

Study Overview
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Brief Summary
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To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of BMS-833923 administered alone, in combination with lenalidomide plus dexamethasone, or in combination with bortezomib in subjects with relapsed or refractory multiple myeloma.

Official Title
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A Phase Ib Multiple Ascending Dose Study of BMS-833923 Alone or in Combination With Lenalidomide (Revlimid) Plus Dexamethasone or in Combination With Bortezomib (Velcade) in Subjects With Relapsed or Refractory Multiple Myeloma

Conditions
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Advanced Cancer, Various, NOS

Intervention / Treatment
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* Drug: BMS-833923
* Drug: Lenalidomide
* Drug: Dexamethasone
* Drug: Bortezomib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of Multiple Myeloma Men and Women at least 18 years old ECOG status 0-2 Last therapeutic or diagnostic treatment at least 21 days prior Bone marrow transplants must have been completed at least 3 months prior Any toxicity from prior therapies must have resolved to Grade ≤1 Exclusion Criteria: Women pregnant or breastfeeding WOCBP unwilling/unable to use acceptable method to avoid pregnancy Uncontrolled medical disorder or active infection Current or recent (w/in 3 months) gastrointestinal disorder Inability to swallow oral medication Inability to be venipunctured Uncontrolled or significant cardiovascular disease Uncontrolled hyperlipidemia Intolerance of lenalidomide or bortezomib if participating in Arms B and C Concurrent therapy with any other investigational product Subjects involuntary incarcerated Subjects detained for treatment of psychiatric or physical illness

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 1<br>BMS-833923 (Starting dose is a loading dose of 60 mg for 7 days with a 30 mg daily dose thereafter) | Drug: BMS-833923<br>* Capsule, Oral, Once daily, 6 months<br>|
| Active Comparator: Arm 2<br>BMS-833923 (MTD or below) Lenalidomide (at or below the recommended prescribing dose) Dexamethasone (40 mg) | Drug: BMS-833923<br>* Capsule, Oral, Once daily, 6 months<br>Drug: Lenalidomide<br>* Capsule, Oral, Once daily, 6 months<br>* Other names: Revlimid;Drug: Dexamethasone<br>* Capsule, Oral, Once a week, 6 months<br>|
| Active Comparator: Arm 3<br>BMS-833923 (MTD or below) Bortezomib (at or below the recommended prescribing dose) | Drug: BMS-833923<br>* Capsule, Oral, Once daily, 6 months<br>Drug: Bortezomib<br>* Powder, IV, On days 1, 4, 8, 11, 6 months<br>* Other names: Velcade;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To establish DLT(s), MTD, and Phase 2 dose range and schedule of BMS-833923 administered alone, in combination with two dose levels of lenalidomide plus dexamethasone, or with two dose levels of bortezomib in subjects with relapsed or refractory MM |  | For Treatment Arms A and B, outcome would be measured for approximately 5 months on Days 1, 8, 15, and 28 for Cycles 1 and 2 and then every 28 days for the following cycles | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and tolerability of BMS-833923 as a single agent or in combination with two dose levels of lenalidomide plus a fixed low-dose of dexamethasone or in combination with two dose levels of bortezomib |  | For Treatment Arms A and B, outcome would be measured for approximately 5 months on Days 1, 8, 15, and 28 for Cycles 1 and 2 and then every 28 days for the following cycles | 
| To evaluate the Pharmacokinetics of BMS-833923 |  | For Treatment Arms A and B, outcome would be measured for approximately 5 months on Days 1, 8, 15, and 28 for Cycles 1 and 2 and then every 28 days for the following cycles | 
| To evaluate the Pharmacodynamics effects of BMS-833923 |  | For Treatment Arms A and B, outcome would be measured for approximately 5 months on Days 1, 8, 15, and 28 for Cycles 1 and 2 and then every 28 days for the following cycles |