PH III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Previously Untreated Multiple Myeloma (ELO 1 Substudy)

Study Overview
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Brief Summary
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The purpose of the study is to look at subjects who receive Lenalidomide, Dexamethasone, and Elotuzumab and determine if they will have lower surface CS1 expression on malignant plasma cells at the time of progression than those who receive Lenalidomide and Dexamethasone without Elotuzumab

Official Title
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A Phase 3, Randomized, Open Label Trial of Lenalidomide/Dexamethasone With or Without Elotuzumab in Subjects With Previously Untreated Multiple Myeloma

Conditions
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Newly Diagnosed, Previously Untreated Multiple Myeloma

Intervention / Treatment
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* Drug: Lenalidomide
* Drug: Dexamethasone
* Biological: Elotuzumab


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 who are newly diagnosed with symptomatic MM and who: Have not received any prior systemic anti-myeloma therapy Have measurable disease And are not candidates for high-dose therapy plus stem-cell transplantation (SCT) because of age (≥65 years) or coexisting conditions. Refusal to undergo high dose therapy with SCT is NOT sufficient for entry onto CA204-006 for a subject <65 years old. There must be a comorbidity that prevents SCT for a subject <65 years old Exclusion Criteria: Subjects with non-secretory or oligo-secretory or free light-chain only myeloma Smoldering MM, defined as asymptomatic MM with absence of lytic bone lesions Monoclonal Gammopathy of Undetermined Significance (MGUS) 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Lenalidomide + Dexamethasone<br>Lenalidomide 25 mg capsules by mouth once daily (on Days 1-21), repeat every 28 days until subject meets criteria for discontinuation of study drug Dexamethasone 40 mg tablets by mouth weekly (on Days 1, 8, 15, 22), repeat every 28 days until subject meets criteria for discontinuation of study drug | Drug: Lenalidomide<br> <br> * Other names: Revlimid®;Drug: Dexamethasone<br> <br> * Other names: Taperpak®;|
| Experimental: Arm 2: Lenalidomide + Dexamethasone + Elotuzumab<br>Lenalidomide 25 mg capsules by mouth once daily (Days 1-21) Dexamethasone 28 mg tablets by mouth once daily [Days 1, 8, 15, 22 (cycles 1 & 2); Days 1 & 15(cycles 3-18); Day 1 (cycle 19 & beyond)] Dexamethasone 40 mg tablets by mouth once daily [Days 8 & 22 (cycles 3-18); Days 8, 15, 22 (cycle 19 & beyond)] Dexamethasone 8 mg IV (intravenous) solution once daily [Days 1, 8, 15, 22 (cycles 1 & 2); Days 1 & 15 (cycles 3-18); Day 1 (cycle 19 & beyond)] Elotuzumab 10 mg/kg IV solution weekly [Days 1, 8, 15, 22 (cycles 1 & 2); Days 1 & 15 (cycles 3-18)] Elotuzumab 20 mg/kg IV solution on Day 1 (cycle 19 & beyond) Repeat above-mentioned dose cycles every 28 days until subject meets criteria for discontinuation of study drug | Drug: Lenalidomide<br> <br> * Other names: Revlimid®;Drug: Dexamethasone<br> <br> * Other names: Taperpak®;Biological: Elotuzumab<br> <br> * Other names: BMS-901608;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Progression of the Cell Surface Expression of CS1 From Bone Marrow-Derived Multiple Myeloma (MM) Cells | CS1 (CD2 subset-1, also known as CRACC, SLAMF7, CD319) expression levels in multiple myeloma cells were analyzed from bone-marrow aspirates collected at baseline and at time of progression through mean fluorescent intensity. The following conditions were considered to describe multiple myeloma cells expressing CS1 (CS1+/CD38++/CD138+/CD56+/CD19-/CD45DIM) | From baseline (screening) to time of progression (up to approximately 54 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Bone Marrow-Derived Multiple Myeloma (MM) Cells Expressing Cell Surface CS1 at Time of Progression | CS1 (CD2 subset-1, also known as CRACC, SLAMF7, CD319) expression levels in multiple myeloma cells were analyzed from bone-marrow aspirates collected at time of progression. The following conditions were considered to describe multiple myeloma cells expressing CS1 (CS1+/CD38++/CD138+/CD56+/CD19-/CD45DIM) | Time of progression (up to approximately 54 months from pre-treatment screening) | 
| Levels of CS1 Soluble Form (sCS1) in Serum | Expression levels of the free form of soluble CS1 were analyzed at different timepoints from serum samples derived from peripheral blood collection | At baseline (screening), during main study therapy (cycle 3 day 1, up to 64 days) and at time of progression (up to approximately 31 months) | 
| Change From Baseline in the Levels of CS1 Soluble Form (sCS1) in Serum During Therapy and At Progression | Expression levels of the free form of soluble CS1 were analyzed at different timepoints from serum samples derived from peripheral blood collection | From baseline (screening) to cycle 3 day 1 of the main study therapy (up to 64 days) and from baseline (screening) to time of progression (up to approximately 31 months) | 
| Change From Baseline in the Number of Circulating Multiple Myeloma (MM) Cells | Circulating MM cells isolated from peripheral blood | From baseline (screening) to cycle 3 day 1 of the main study therapy (up to 64 days) and from baseline (screening) to the time of progression (up to approximately 54 months) | 
| Change From Baseline in Cell Surface CS1 Expression Levels in Circulating Multiple Myeloma (MM) Cells | Circulating MM cells isolated from peripheral blood | From baseline (screening) to cycle 3 day 1 of the main study therapy (up to 64 days) and from baseline (screening) to the time of progression (up to approximately 54 months) | 
| CS1 Expression Levels in Matched Samples of Bone Marrow-Derived Multiple Myeloma (MM) Cells and Circulating MM Cells | CS1 expression levels analyzed from matching bone marrow aspirates (for bone marrow-derived MM cells) and from peripheral blood (for circulating tumor cells) collected from the same participants | At baseline (screening), during main study therapy (cycle 3 day 1) and at time of progression (up to approximately 54 months) |