Phase III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Newly Diagnosed, Previously Untreated 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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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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Multiple Myeloma

Intervention / Treatment
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* Drug: Lenalidomide
* Drug: Dexamethasone
* Drug: Dexamethasone
* Drug: Dexamethasone
* Drug: Dexamethasone
* Biological: Elotuzumab (BMS-901608; HuLuc63)
* 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: Subjects who are newly diagnosed with symptomatic Multiple Myeloma (MM) and who: have not received any prior systemic anti-myeloma therapy AND 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 CA204006 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: 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<br>* Tablets, Oral, 28 mg, once daily, on Days 1, 8, 15, 22 (cycles 1&2) ; Days 1 &15 (cycles 3-18); Day 1 (cycle 19 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug<br>* Other names: Taperpak®;Drug: Dexamethasone<br>* Tablets, Oral, 40 mg, once daily, on Days 8 & 22 (cycles 3-18); Days 8, 15, 22 (cycle 19 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug<br>* Other names: Taperpak®;Drug: Dexamethasone<br>* Solution, Intravenous (IV), 8 mg, Once daily, on Days 1, 8, 15, 22 (cycles 1&2) ; Days 1 &15 (cycles 3-18); Day 1 (cycle 19 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug<br>* Other names: Taperpak®;Biological: Elotuzumab (BMS-901608; HuLuc63)<br>* Solution, Intravenous (IV), 10 mg/kg, weekly, on Days 1, 8, 15, 22 (cycles 1&2); Days 1 and 15 (cycles 3-18), Repeat every 28 days until subject meets criteria for discontinuation of study drug<br>Biological: Elotuzumab (BMS-901608; HuLuc63)<br>* Solution, Intravenous (IV), 20 mg/kg, Day 1 (cycle 19 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 |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS is defined as the time from randomization to the date of the first documented tumor progression (as determined by the Independent Review Committee (IRC)) or death due to any cause. The IRC conducted a blinded, independent review of the tumor assessments based on the European Group for Blood and Bone Marrow Transplant (EBMT) criteria. Censoring rules applied: Participants receiving subsequent systemic anti-myeloma therapy prior to documented progression were censored at the date of the last adequate tumor assessment prior to new therapy. Participants who had an event (progression or death) > 10 weeks after their last tumor assessment were censored at their last adequate tumor assessment prior to the event. Participants without progression or death (and not receiving subsequent therapy prior to progression) were censored at their last adequate tumor assessment. Participants without any post-baseline tumor assessments were censored on the date of randomization | From randomization to date of first documented tumor progression or death due to any cause (up to 8 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is defined as the percentage of participants with objective response among all randomized subjects. Participants with an objective response are those participants experiencing a partial response (PR) or better, based on Independent Review Committee (IRC) assessment, as per EBMT criteria. | From randomization to primary completion date (approximately 8 years) | 
| Overall Survival (OS) | Survival is defined as the time from randomization to the date of death. A participant who did not die had his or her survival duration censored at the date of last contact ('last known date alive). | From randomization to the date of death (up to 8 years) | 
| Mean Change From Baseline of Pain Severity Score and Pain Interference Score | Pain severity (sensory dimension) and pain interference (reactive dimension, assessing the degree to which pain interferes with function) are measured using the Brief Pain Inventory- Short Form (BPI-SF). BPI-SF numeric rating scale goes from 0 (No pain) to 10 (Pain as bad as you can imagine). | From Baseline to End of Treatment (approximately 8 years) | 
| Progression Free Survival (PFS) Rate at Specific Time-points | PFS rate is defined as the percentage of participants experiencing PFS at the defined time-points. | From randomization to the specified time-point (up to 5 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Newly Diagnosed, Previously Untreated