Phase III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of the study is to determine whether the addition of Elotuzumab to Lenalidomide/low-dose Dexamethasone will increase the progression free survival (PFS).

Official Title
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Phase 3, Randomized, Open Label Trial of Lenalidomide/Dexamethasone With or Without Elotuzumab in Relapsed or Refractory Multiple Myeloma (MM)

Conditions
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Lymphoma, Multiple Myeloma

Intervention / Treatment
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* Drug: Lenalidomide
* Drug: Dexamethasone
* Drug: Dexamethasone (Oral)
* Drug: Dexamethasone (IV)
* Biological: Elotuzumab (BMS-901608; HuLuc63)


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: Documented progression from most recent line of therapy 1-3 prior lines of therapy Measurable disease Life expectancy ≥3 months Prior treatment with Lenalidomide permitted if: Best response achieved was ≥Partial Response (PR) Patient was not refractory Patient did not discontinue due to a Grade ≥3 related adverse event Subject did not receive more than 9 cycles of Lenalidomide and had at least 9 months between the last dose of Lenalidomide and progression Exclusion Criteria: Subjects with non-secretory or oligo-secretory or serum free light-chain only myeloma Active plasma cell leukemia Known Human immunodeficiency virus (HIV) infection or active hepatitis A, B, or C

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lenalidomide + Dexamethasone<br> | Drug: Lenalidomide<br>* Capsules, Oral, 25 mg, once daily, on Days 1-21, Repeat every 28 days until subject meets criteria for discontinuation of study drug<br>* Other names: Revlimid®;Drug: Dexamethasone<br>* Tablets, Oral, 40 mg, weekly, on Days 1, 8, 15, 22, Repeat every 28 days until subject meets criteria for discontinuation of study drug<br>* Other names: Taperpak®;|
| Experimental: Lenalidomide + Dexamethasone +Elotuzumab<br> | Drug: Lenalidomide<br>* Capsules, Oral, 25 mg, once daily, on Days 1-21, Repeat every 28 days until subject meets criteria for discontinuation of study drug<br>* Other names: Revlimid®;Drug: Dexamethasone (Oral)<br>* On weeks without Elotuzumab dosing: Tablets, Oral, 40mg, Repeat every 28 days until subject meets criteria for discontinuation of study drug. On weeks with Elotuzumab dosing: Tablets, Oral, 28 mg, Repeat every 28 days until subject meets criteria for discontinuation of study drug<br>* Other names: Taperpak®;Drug: Dexamethasone (IV)<br>* On weeks without Elotuzumab dosing: Not Applicable (N/A) On weeks with Elotuzumab dosing: Solution, Intravenous (IV), 8 mg, weekly, Repeat every 28 days until subject meets criteria for discontinuation of study drug<br>* Other names: Taperpak®;Biological: Elotuzumab (BMS-901608; HuLuc63)<br>* Solution, IV, 10 mg/kg, weekly, on Days 1, 8, 15, 22 (cycles 1&2); Days 1 and 15 (cycles 3 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Progression Free Survival (PFS) | Primary definition of Progression-free survival (PFS) defined as the time from randomization to the date of first documented tumor progression or death due to any cause. Participants were censored at the last adequate assessment prior to the start of any subsequent systemic-therapy or at the last adequate assessment prior to 2 missing assessments (> 10 weeks). Participants who died more than 10 weeks after the randomization date and had no on-treatment assessment were censored at the randomization date. Clinical deterioration was not considered progression. The primary analysis of PFS was based on the primary definition using the Independent Review Committee (IRC) tumor assessment using the European Group for Blood and Bone Marrow Transplant (EBMT) criteria. Tumor assessments were made every 4 weeks (±1 week) relative to the first dose of study medication. | From randomization up to 326 events (up to approximately 38 months) | 
| Objective Response Rate (ORR) | Objective response rate (ORR) defined as the percentage of participants with a best response on-study of partial response (PR) or better (stringent CR [sCR], complete response [CR], very good partial response [VGPR], and partial response [PR]) based on the Independent Review Committee (IRC) assessment of best response using the European Group for Blood and Bone Marrow Transplant (EBMT) assessment criteria. Participants were censored at the last adequate assessment prior to the start of any subsequent systemic-therapy or at the last adequate assessment prior to 2 missing assessments (> 10 weeks). Participants who died more than 10 weeks after the randomization date and had no on-treatment assessment were censored at the randomization date. Clinical deterioration was not considered progression. Assessments were made every 4 weeks. | From randomization up to approximately 38 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Overall Survival (OS) | Overall survival is defined as the time from randomization to the date of death from any cause. If a subject has not died, their survival time will be censored at the date of last contact (last known alive date). A subject will be censored at the date of randomization if they were randomized but had no follow-up. (Based on Kaplan Meier estimates) | Randomization to the date of death from any cause (up to approximately 9 years) | 
| Change From Baseline of Mean Score Pain Severity (BPI-SF) | The change from baseline of the mean score of pain severity at the end of treatment using the Brief Pain Inventory-Short Form (BPI-SF). The BPI-SF is a self administered questionnaire developed to assess the severity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI-SF uses 0 (No pain, No interference) to 10 (Pain as bad as you can imagine, Highest imaginable interference) numeric rating scale. | From baseline up to approximately 38 months | 
| Change From Baseline of Mean Score Pain Interference (BPI-SF) | The change from baseline of the mean score of pain interference at the end of treatment using the Brief Pain Inventory-Short Form (BPI-SF). The BPI-SF is a self administered questionnaire developed to assess the severity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI-SF uses 0 (No pain, No interference) to 10 (Pain as bad as you can imagine, Highest imaginable interference) numeric rating scale. | From baseline up to approximately 38 months |