Biomarker Study of Elotuzumab in High Risk Smoldering Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to determine whether elotuzumab will improve response in patients with high risk smoldering myeloma who have more CD56^dim cells (a marker for the health of the body's immune system)

Detailed Description
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Intervention model: Dosing is sequential

Official Title
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A Phase 2 Biomarker Study of Elotuzumab (Humanized Anti-CS1 Monoclonal IgG1 Antibody) Monotherapy to Assess the Association Between NK Cell Status and Efficacy in High Risk Smoldering Myeloma

Conditions
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Smoldering Multiple Myeloma

Intervention / Treatment
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* 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. Key Inclusion Criteria: Participants with a confirmed diagnosis, according to criteria of the International Myeloma Working Group, of smoldering multiple myeloma, considered high risk according to the following: Serum monoclonal (M) protein ≥3 gm/dL and bone marrow plasma cells (BMPC) ≥10% or Serum M protein 1-3 g/dL and BMPC ≥10% and abnormal free light chain ratio of <0.125 or >8.0 Urine M protein >200 mg/24 hours, ≥10% BMPC, and serum free light chain ratio ≤0.125 or ≥8.0 Key Exclusion Criteria: Active multiple myeloma Monoclonal gammopathy of undetermined significance Active plasma cell leukemia Positive for hepatitis B or C virus or HIV infection

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: Elotuzumab, 20 mg/kg<br>Intravenous solution administered in 28-day cycles. Cycle 1: Days 1 and 8. Cycle 2 and beyond: Day 1 only. | Biological: Elotuzumab (BMS-901608; HuLuc63)<br> <br> |
| Experimental: Elotuzumab, 10 mg/kg<br>Intravenous solution administered in 28-day cycles. Cycle 1 and 2: Days 1, 8, 15, and 22. Cycle 3 and beyond: Days 1 and 15. | Biological: Elotuzumab (BMS-901608; HuLuc63)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Linear Regression of Maximal Percent Reduction in Serum Monoclonal (M) Protein on Baseline Percent CD56^Dim Cells in Bone Marrow | Estimated using linear regression model, with baseline CD56^dim cells as the independent covariate, and maximal percent reduction in serum M protein as the dependent variable. For 1 patient who had nonmeasurable disease at baseline, the percent change in serum kappa-lambda difference was used instead of the percent change in serum M protein. Unit of measure=percent change from baseline in M protein cells/ percent change in CD56^dim cells (% chg from BL in M pro/% chg CD56^dim cs) | From day of last patient, first dose to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Infusion Reactions | 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. | From day of last patient, first dose to 6 months | 
| Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality | Clinical laboratory evaluations included hematology, chemistry, and liver and renal functioning. | From date of first dose to date of last dose plus 60 days (assessed up to August 2017, approximately 59 months | 
| Number of Participants With a Dose- or Concentration-related Effect on QTcF Interval, PR Interval, QRS Interval, and Heart Rate | All on-treatment electrocardiograms (ECGs) were performed in triplicates ( 1 ECG test equaled 3 consecutive individual 12-lead ECGs performed within a 4-minute period). The timing of the ECG was critical to the endpoint of the study. The investigative site documented any deviations from the protocol or procedures related to ECG collection or serum sampling. No ECGs were excluded due to timing deviations; no deviations were considered clinically relevant and all ECG data were included. | cycle 1 to first day of cycle 3 assessed up to 08/17, approximately 59 months | 
| Progression Free Survival (PFS) Rate | The probability was estimated from the K-M curve of subjects being alive and without disease progression (modified IMWG criteria) at 2 years from the initiation of study therapy by dose cohort | Up to 2 years from the initiation of study therapy by dose cohort (approximately 24 months) | 
| Objective Response Rate (ORR) | ORR is defined as the number of participants with stringent compete response [SCR], complete response [CR], very good partial response [VGPR], and partial response [PR])/number of participants in arm, expressed as a percentage. Confidence intervals computed using the Clopper and Pearson method. SCR=CR plus normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. CR=Negative immunofixation on serum and urine and 5% or fewer plasma cells in bone marrow. VGPR=Serum and urine monoclonal (M) protein detectable by immunofixation but not on electrophoresis or 90% reduction in serum M protein level plus urine M protein level <100 mg/24 hour. PR=50% reduction of serum M protein and reduction in 24-hour urinary M protein by 90% or to <200 mg/24 hour | From first dose to date of progression or objective response (assessed up to August 2017, approximately 59 months) |