Safety Study of Elotuzumab in Combination With Thalidomide and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and tolerability of elotuzumab administered in combination with thalidomide and dexamethasone in the treatment of relapsed and/or refractory multiple myeloma.

Official Title
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Phase 2a Single-Arm Safety Study of Elotuzumab in Combination With Thalidomide and Dexamethasone in Subjects With Relapsed and/or Refractory Multiple Myeloma

Conditions
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Relapsed and/or Refractory Multiple Myeloma

Intervention / Treatment
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* Biological: Elotuzumab
* Biological: Thalidomide
* Biological: Dexamethasone
* Biological: Cyclophosphamide


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. Key Inclusion Criteria: Confirmed diagnosis of previously treated multiple myeloma with progression documented by criteria of the International Myeloma Working Group after or during the most recent therapy Patient received 5 or fewer prior lines of therapy Eastern Cooperative Oncology Group performance status of 0 or 1 (safety lead-in cohort) or 0 to 2 (additional patients) Measurable disease as defined by at least 1 of the following: Serum immunoglobulin (Ig)G, IgA, IgM, or monoclonal (M) protein level ≥0.5 g/dL or serum IgD M protein level ≥0.05 g/dL; or Urine M protein level ≥200 mg excreted in a 24-hour collection sample; or Involved serum free light chain level ≥10 mg/dL, provided the free light chain ratio is abnormal Key Exclusion Criteria: Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia Monoclonal gammopathy of undetermined significance, smoldering myeloma, or Waldenström's macroglobulinemia Left ventricular ejection fraction by echocardiogram or Multi Gated Acquisition ≤50% Electrocardiogram finding of QTc ≥450 msec Active plasma cell leukemia (defined as either 20% of peripheral white blood cells, composed of plasma/CD138+ cells or an absolute plasma cell count of 2*10^9/L) Diagnosis of nonsecretory myeloma Active hepatitis A, B, or C virus infection Grade ≥2 neuropathy

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Elotuzumab + Thalidomide + Dexamethasone + Cyclophosphamide<br> | Biological: Elotuzumab<br>* Powder for solution, 400-mg vials, for infusion<br>* Other names: HuLuc63;Biological: Thalidomide<br>* 50-mg capsules administered orally<br>* Other names: Thalomid®;Biological: Dexamethasone<br>* 2- and 4-mg tablets (and various other strengths, as needed) administered orally and in 4- and 8-mg/mL (and various other strengths, as needed) solutions for intravenous administration<br>* Other names: Taperpak®;Biological: Cyclophosphamide<br>* 50-mg tablets administered orally<br>* Other names: Neosar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Received Treatment Including Cyclophosphamide and Had Grade 3 or Higher Nonhematologic Adverse Events (AEs) | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or unknown relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. | From the first dose of study drug until the last dose of treatment, including cyclophosphamide treatment | 
| Percentage of All Participants Who Received Treatment Without Cyclophosphamide and Had Grade 3 or Higher Nonhematologic Adverse Events (AEs) | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or unknown relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. | From the first dose of study drug until the earlier of discontinuation from E-Td or the time when cyclophosphamide was initiated | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of All Participants Who Received Treatment Including Cyclophosphamide and Had 1 Dose Reduction or Discontinued Due to an Adverse Event | Elotuzumab dose reduction was not permitted. Thalidomide dose reduction, delay, interruptions, or discontinuation was permitted in the event of toxicity. Dexamethasone dose reduction was also permitted in the event of toxicity and in the setting of infusion reactions;dose delays were allowed as clinically indicated at the discretion of the investigator. Cyclophosphamide dose reduction, delay, interruption, or discontinuation was permitted in the event of toxicity. | From the first dose of study drug until the last dose of treatment, including cyclophosphamide treatment | 
| Percentage of All Participants Who Received Treatment Without Cyclophosphamide and Had 1 Dose Reduction or Discontinued Due to an Adverse Event | Elotuzumab dose reduction was not permitted. Thalidomide dose reduction, delay, interruptions, or discontinuation was permitted in the event of toxicity. Dexamethasone dose reduction was also permitted in the event of toxicity and in the setting of infusion reactions;dose delays were allowed as clinically indicated at the discretion of the investigator. | From the first dose of study drug until the earlier of discontinuation from E-Td or the time when cyclophosphamide was initiated |