Biomarker Study of Elotuzumab in High Risk Smoldering Myeloma

• ClinicalTrials.gov Identifier: NCT01441973
• Recruitment Status: Completed
• First Posted: September 28, 2011
• Results First Posted: January 29, 2016
• Last Update Posted: January 23, 2018
• Sponsor: Bristol-Myers Squibb
• Collaborator: AbbVie
• Information provided by (Responsible Party): Bristol-Myers Squibb

Study Description

Brief Summary:

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)

Condition or disease	Intervention/treatment	Phase
Smoldering Multiple Myeloma	Biological: Elotuzumab (BMS-901608; HuLuc63)	Phase 2

Detailed Description:

Intervention model: Dosing is sequential

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 41 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 28, 2011
• Actual Primary Completion Date: May 30, 2014
• Actual Study Completion Date: January 17, 2017

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. Linear Regression of Maximal Percent Reduction in Serum Monoclonal (M) Protein on Baseline Percent CD56^Dim Cells in Bone Marrow [ Time Frame: From day of last patient, first dose to 6 months ]
   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)

Secondary Outcome Measures :

1. Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Infusion Reactions [ Time Frame: From day of last patient, first dose to 6 months ]
   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.
2. Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality [ Time Frame: From date of first dose to date of last dose plus 60 days (assessed up to August 2017, approximately 59 months ]
   Clinical laboratory evaluations included hematology, chemistry, and liver and renal functioning.
3. Number of Participants With a Dose- or Concentration-related Effect on QTcF Interval, PR Interval, QRS Interval, and Heart Rate [ Time Frame: cycle 1 to first day of cycle 3 assessed up to 08/17, approximately 59 months ]
   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.
4. Progression Free Survival (PFS) Rate [ Time Frame: Up to 2 years from the initiation of study therapy by dose cohort (approximately 24 months) ]
   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
5. Objective Response Rate (ORR) [ Time Frame: From first dose to date of progression or objective response (assessed up to August 2017, approximately 59 months) ]
   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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

Sharp Clinical Oncology Research

San Diego, California, United States, 92123

United States, Connecticut

Yale University School Of Medicine

New Haven, Connecticut, United States, 06520

Va Connecticut Healthcare System

West Haven, Connecticut, United States, 06516

United States, Georgia

Winship Cancer Institute.

Atlanta, Georgia, United States, 30322

United States, Illinois

University Of Chicago Medical Center

Chicago, Illinois, United States, 60637

United States, Indiana

Investigative Clinical Research Of Indiana, Llc

Indianapolis, Indiana, United States, 46260

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Missouri

Washington University School Of Medicine

Saint Louis, Missouri, United States, 63110

United States, New York

Weill Cornell Medical College

New York, New York, United States, 10021

Mount Sinai Medical Center

New York, New York, United States, 10029

United States, North Dakota

Mid Dakota Clinic, Pc

Bismarck, North Dakota, United States, 58501

Sponsors and Collaborators

Bristol-Myers Squibb

AbbVie

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trial Patient Recruiting 

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT01441973
• Other Study ID Numbers: CA204-011
• First Posted: September 28, 2011
• Results First Posted: January 29, 2016
• Last Update Posted: January 23, 2018
• Last Verified: December 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Smoldering Multiple Myeloma; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Precancerous Conditions; Hypergammaglobulinemia; Elotuzumab; Antineoplastic Agents