Biomarker Study of Elotuzumab in High Risk Smoldering Myeloma
Primary Purpose
Smoldering Multiple Myeloma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Elotuzumab (BMS-901608; HuLuc63)
Sponsored by
About this trial
This is an interventional treatment trial for Smoldering Multiple Myeloma
Eligibility 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
Sites / Locations
- Sharp Clinical Oncology Research
- Yale University School Of Medicine
- Va Connecticut Healthcare System
- Winship Cancer Institute.
- University Of Chicago Medical Center
- Investigative Clinical Research Of Indiana, Llc
- Dana Farber Cancer Institute
- Dana-Farber Cancer Institute
- Washington University School Of Medicine
- Weill Cornell Medical College
- Mount Sinai Medical Center
- Mid Dakota Clinic, Pc
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Elotuzumab, 20 mg/kg
Elotuzumab, 10 mg/kg
Arm Description
Intravenous solution administered in 28-day cycles. Cycle 1: Days 1 and 8. Cycle 2 and beyond: Day 1 only.
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.
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
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.
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.
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.
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
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
Full Information
NCT ID
NCT01441973
First Posted
September 27, 2011
Last Updated
December 21, 2017
Sponsor
Bristol-Myers Squibb
Collaborators
AbbVie
1. Study Identification
Unique Protocol Identification Number
NCT01441973
Brief Title
Biomarker Study of Elotuzumab in High Risk Smoldering Myeloma
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
December 28, 2011 (Actual)
Primary Completion Date
May 30, 2014 (Actual)
Study Completion Date
January 17, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb
Collaborators
AbbVie
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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)
Detailed Description
Intervention model: Dosing is sequential
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Smoldering Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Elotuzumab, 20 mg/kg
Arm Type
Experimental
Arm Description
Intravenous solution administered in 28-day cycles. Cycle 1: Days 1 and 8. Cycle 2 and beyond: Day 1 only.
Arm Title
Elotuzumab, 10 mg/kg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Elotuzumab (BMS-901608; HuLuc63)
Primary Outcome Measure Information:
Title
Linear Regression of Maximal Percent Reduction in Serum Monoclonal (M) Protein on Baseline Percent CD56^Dim Cells in Bone Marrow
Description
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)
Time Frame
From day of last patient, first dose to 6 months
Secondary Outcome Measure Information:
Title
Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Infusion Reactions
Description
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.
Time Frame
From day of last patient, first dose to 6 months
Title
Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality
Description
Clinical laboratory evaluations included hematology, chemistry, and liver and renal functioning.
Time Frame
From date of first dose to date of last dose plus 60 days (assessed up to August 2017, approximately 59 months
Title
Number of Participants With a Dose- or Concentration-related Effect on QTcF Interval, PR Interval, QRS Interval, and Heart Rate
Description
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.
Time Frame
cycle 1 to first day of cycle 3 assessed up to 08/17, approximately 59 months
Title
Progression Free Survival (PFS) Rate
Description
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
Time Frame
Up to 2 years from the initiation of study therapy by dose cohort (approximately 24 months)
Title
Objective Response Rate (ORR)
Description
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
Time Frame
From first dose to date of progression or objective response (assessed up to August 2017, approximately 59 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Sharp Clinical Oncology Research
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Yale University School Of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Va Connecticut Healthcare System
City
West Haven
State/Province
Connecticut
ZIP/Postal Code
06516
Country
United States
Facility Name
Winship Cancer Institute.
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University Of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Investigative Clinical Research Of Indiana, Llc
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Washington University School Of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Mid Dakota Clinic, Pc
City
Bismarck
State/Province
North Dakota
ZIP/Postal Code
58501
Country
United States
12. IPD Sharing Statement
Links:
URL
http://bms.com/studyconnect/Pages/home.aspx
Description
BMS Clinical Trial Patient Recruiting
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Biomarker Study of Elotuzumab in High Risk Smoldering Myeloma
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