Study of Elotuzumab in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma and Various Levels of Renal Function
PH Ib Study of Elotuzumab in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma and Normal Renal Function, Severe Renal Impairment, or End Stage Renal Disease Requiring Dialysis
1 other identifier
interventional
35
1 country
11
Brief Summary
The purpose of the study is to assess the concentration of Elotuzumab in Myeloma patients with very low kidney function including patients on dialysis.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 multiple-myeloma
Started Jan 2012
Typical duration for phase_1 multiple-myeloma
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 12, 2011
CompletedFirst Posted
Study publicly available on registry
July 14, 2011
CompletedStudy Start
First participant enrolled
January 6, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 21, 2014
CompletedResults Posted
Study results publicly available
January 27, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
July 18, 2016
CompletedAugust 3, 2017
June 1, 2017
2.2 years
July 12, 2011
December 18, 2015
June 27, 2017
Conditions
Outcome Measures
Primary Outcomes (2)
Geometric Mean Maximum Observed Serum Concentration (Cmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
The quantification of elotuzumab in human serum was performed using a validated Enzyme-linked immunoassay (ELISA). Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. Cmax was measured in micrograms per milliliter (µg/mL). Pharmacokinetic (PK) parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value \< 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.
Day 1 of Cycle 1 to 28 days post dose
Geometric Mean Area Under Serum Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration AUC(0-T) and From Time Zero Extrapolated to Infinite Time AUC(INF) of Elotuzumab Following Cycle 1, Day 1 - Grouping by C-G CrCl Method
The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD participants had 2 additional sample times: immediately prior to and immediately after dialysis. AUC was measured in µg\*h/mL. PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value \< 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group
Day 1 of Cycle 1 to 28 days post dose
Secondary Outcomes (5)
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died
From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose.
From first dose (Day 1) to last dose plus 60 days, up to Primary Endpoint (June 2014), approximately 2 years
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests
From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests
From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests
From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
Other Outcomes (4)
Mean Terminal-phase Elimination Half-life (T-Half) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
Day 1 of Cycle 1 to 28 days post dose
Median Time to Maximal Concentration (Tmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
Day 1 of Cycle 1 to 28 days post dose
Geometric Mean Total Body Clearance (CLT) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
Day 1 of Cycle 1 to 28 days post dose
- +1 more other outcomes
Study Arms (3)
Arm 1: Lenalidomide + Dexamethasone +Elotuzumab
EXPERIMENTALSevere Renal Impairment
Arm 2: Lenalidomide + Dexamethasone +Elotuzumab
EXPERIMENTALEnd-stage renal disease
Arm 3: Lenalidomide + Dexamethasone +Elotuzumab
EXPERIMENTALNormal renal function
Interventions
Capsules, Oral, 15 mg, One capsule every 48 hours through Days 1-21 (Repeat every 28 days until subject meets criteria for discontinuation of study drug
Tablets, Oral, 28 mg weekly, on day 1 (cycle 1); days 1, 8, 15, 22 (cycles 2-3; days 1 \&15 (cycle 4 and beyond) Repeat every 28 days until subject meets criteria for discontinuation of study drug
Solution, Intravenous, 10 mg/kg, weekly, on day 1 (cycle 1); days 1, 8, 15, 22 (cycles 2-3; days 1 \&15 (cycle 4 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug
Eligibility Criteria
You may qualify if:
- Subjects with Multiple Myeloma (MM) and renal function fitting one of three categories:
- Severe renal impairment: estimated creatinine clearance (CrCl) \<30 ml/min, but not requiring dialysis
- End-stage renal disease: requiring hemodialysis
- Normal renal function: estimated CrCl ≥90 ml/min
- Documented evidence of symptomatic MM, either newly diagnosed or relapsed/refractory
- Prior Lenalidomide exposure is permitted only if the subject did not discontinue Lenalidomide due to a Grade ≥3 related Adverse Event (AE)
You may not qualify if:
- Monoclonal Gammopathy of Undetermined Significance (MGUS), Waldenstrom's macroglobulinemia, or smoldering myeloma
- Active plasma cell leukemia
- All adverse events of any prior chemotherapy, surgery, or radiotherapy not resolved
- POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Acute renal failure
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Bristol-Myers Squibblead
- AbbViecollaborator
Study Sites (11)
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322, United States
Investigative Clinical Research Of Indiana, Llc
Indianapolis, Indiana, 46260, United States
University Of Iowa Hospitals And Clinics
Iowa City, Iowa, 52242, United States
University Of Maryland
Baltimore, Maryland, 21201, United States
Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Washington University School Of Medicine
St Louis, Missouri, 63110, United States
Weill Cornell Medical College
New York, New York, 10021, United States
Mount Sinai Medical Center
New York, New York, 10029, United States
Tennessee Oncology, Pllc
Nashville, Tennessee, 37203, United States
The University Of Texas M.D. Anderson Cancer Center
Houston, Texas, 77030, United States
Va Puget Sound Health Care System
Seattle, Washington, 98108, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Bristol-Myers Squibb Study Director
- Organization
- Bristol-Myers Squibb
Study Officials
- STUDY DIRECTOR
Bristol-Myers Squibb
Bristol-Myers Squibb
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 12, 2011
First Posted
July 14, 2011
Study Start
January 6, 2012
Primary Completion
March 21, 2014
Study Completion
July 18, 2016
Last Updated
August 3, 2017
Results First Posted
January 27, 2016
Record last verified: 2017-06