Biomarker Study of Elotuzumab in High Risk Smoldering Myeloma

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

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)

Study Overview

• Status: Completed
• Conditions: Smoldering Multiple Myeloma
• Intervention / Treatment: Biological: Elotuzumab (BMS-901608; HuLuc63)

Detailed Description

Intervention model: Dosing is sequential

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • Sharp Clinical Oncology Research
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
    • West Haven, Connecticut, United States, 06516
      • VA Connecticut Healthcare System
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute.
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Investigative Clinical Research of Indiana, LLC
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic, PC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Elotuzumab, 20 mg/kg; 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)
Experimental: Elotuzumab, 10 mg/kg; 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)

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: AbbVie

Publications and helpful links

Helpful Links

• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2011
• Primary Completion (Actual): May 30, 2014
• Study Completion (Actual): January 17, 2017

Study Registration Dates

• First Submitted: September 27, 2011
• First Submitted That Met QC Criteria: September 27, 2011
• First Posted (Estimate): September 28, 2011

Study Record Updates

• Last Update Posted (Actual): January 23, 2018
• Last Update Submitted That Met QC Criteria: December 21, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Precancerous Conditions; Hypergammaglobulinemia; Multiple Myeloma; Neoplasms, Plasma Cell; Smoldering Multiple Myeloma; Antineoplastic Agents; Elotuzumab
• Other Study ID Numbers: CA204-011

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No