Study of Elotuzumab in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma and Various Levels of Renal Function
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT01393964
- Lead Sponsor
- Bristol-Myers Squibb
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 35
-
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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 3: Lenalidomide + Dexamethasone +Elotuzumab Lenalidomide Normal renal function Arm 1: Lenalidomide + Dexamethasone +Elotuzumab Elotuzumab (BMS-901608; HuLuc63) Severe Renal Impairment Arm 2: Lenalidomide + Dexamethasone +Elotuzumab Lenalidomide End-stage renal disease Arm 2: Lenalidomide + Dexamethasone +Elotuzumab Elotuzumab (BMS-901608; HuLuc63) End-stage renal disease Arm 3: Lenalidomide + Dexamethasone +Elotuzumab Elotuzumab (BMS-901608; HuLuc63) Normal renal function Arm 1: Lenalidomide + Dexamethasone +Elotuzumab Lenalidomide Severe Renal Impairment Arm 1: Lenalidomide + Dexamethasone +Elotuzumab Dexamethasone Severe Renal Impairment Arm 2: Lenalidomide + Dexamethasone +Elotuzumab Dexamethasone End-stage renal disease Arm 3: Lenalidomide + Dexamethasone +Elotuzumab Dexamethasone Normal renal function
- Primary Outcome Measures
Name Time Method Geometric Mean Maximum Observed Serum Concentration (Cmax) 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 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.
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 Day 1 of Cycle 1 to 28 days post dose 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
- Secondary Outcome Measures
Name Time Method 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) 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 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 Serum samples were evaluated for the presence of ADAs using a validated bridging electrochemiluminescence (ECL) immunoassay. Samples in: Cycle 1, Day 1 0 h (pre-dose), Cycle 2, Day 1(Study Day 29), 0 h (pre-dose; 672 h post-dose), Cycle 3, Day 1, 0 h and in cycle thereafter, at end of study/discontinuation, and at 30 and 60 day follow up visits post treatment. ADA Positive Participant: baseline negative with at least one ADA positive sample at any time after initiation of treatment or baseline positive with at least one ADA positive sample at any time after initiation of treatment with a titer 9-fold greater than the baseline; Persistent Positive: ADA positive at 2 or more sequential timepoints at least 12 weeks apart; Last Sample Positive: Not persistent positive and ADA Positive Sample in the last sampling timepoint; Other Positive: not persistent positive with ADA negative sample in the last sampling; ADA Negative: no ADA positive sample after the initiation of treatment.
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) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Hemoglobin Gr 1:\<LLN to 10.0 g/dL, Gr 2:\<10.0 to 8.0 g/dL, Gr 3:\<8.0 to 6.5 g/dL, Gr 4:\<6.5 g/dL. Lymphocytes absolute (abs) Gr 1: \<1.5 to 0.8 \*10\^3 c/µL, Gr 2 \<0.8 to 0.5 \*10\^3 c/µL, Gr 3: \<0.5 to 0.2 \*10\^3 c/µL, Gr 4: \<0.2\*10\^3 c/µL. Neutrophils abs: Gr 1:\<LLN to 1.5\*10\^9/L, Gr 2:\<1.5 to 1.0\*10\^9/L, Gr 3:\<1.0 to 0.5\*10\^9/L, Gr 4:\<0.5\*10\^9/L. Platelet count Gr 1:LLN to 75.0\*10\^9/L, Gr 2:\<75.0 to 50.0\*10\^9/L, Gr 3:\<50.0 to 25.0\*10\^9/L, Gr 4:\<25.0 to 10\^9/L. Leukocytes Gr 1:\<LLN to 3.0 \*10\^3 c/µL, Gr 2; \<3.0 to 2.0 \*10\^3 c/µL, Gr 3: \<2.0 to 1.0 \*10\^3 c/µL, Gr 4: \<1.0 \*10\^3 c/µL.
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) NCI CTCAE, version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Upper Limits of Normal (ULN). Alanine transaminase (ALT); Aspartate aminotransferase (AST); Alkaline phosphatase (ALP). ALT Grade (Gr)1:\>1.0 to 2.5\*ULN; Gr 2: \>2.5 to 5.0\*ULN; Gr 3: \>5.0 to 20.0\*ULN; Gr 4: \>20.0\*ULN. AST Gr 1: \>1.0 to 2.5\*ULN; Gr 2: \>2.5 to 5.0\*ULN; Gr 3: \>5.0 to 20.0\*ULN; Gr 4: \>20.0\*ULN. Total bilirubin Gr 1: \>1.0 to 1.5\*ULN; Gr 2: \>1.5 to 3.0\*ULN; Gr 3: \>3.0 to 10..0\*ULN; Gr 4: \>10.0.0\*ULN. ALP (U/L) Gr1:\>1.0 to 2.5\*ULN, Gr2:\>2.5 to 5.0\*ULN, Gr3:\>5.0 to 20.0\*ULN, Gr4:\>20.0\*ULN. Albumin (low) Gr 1:\<LLN to 3 grams per deciliter (g/dL); Gr 2: \<3.0 - 2.0 g/L; Gr 3: \< 2 g/dL. Creatinine Gr 1: \>1 - 1.5\*baseline (BL)to \>ULN - 1.5\*ULN; Gr 2: \>1.5 - 3.0\*BL to \> 1.5 - 3.0\*ULN; Gr 3: \>3.0\*BL to \> 3.0 - 6.0\*ULN; Gr 4: \>6.0\*ULN.
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) Sodium high (H) Gr 1:\>ULN - 150; Gr 2: \>150 - 155; Gr 3: \>155 - 160; Gr 4: \>160 mmol/L; Sodium low(L) Gr 1:\<LLN - 130; Gr 3: \<130 - 120; Gr 4: \<120 mmol/L. Potassium (H) Gr 1: \>ULN - 5.5; Gr 2: \>5.5 - 6.0; Gr 3: \> 6.0 - 7.0; Gr 4: \>7.0 mmol/L; Potassium (L) Gr 1: \<LLN - 3.0; Gr 2: \<LLN - 3.0; Gr 3: \< 3.0 - 2.5; Gr 4: \<2.5 mmol/L. Bicarbonate Gr1: 16-\<LLN, Gr2: 11-16, Gr3, 8-11, Gr4: \<8 milliequivalents per liter (mEq/L). Phosphorus Gr 1: 2.5 - \<LLN, Gr2 2.0-\<2.5, Gr3: 1.0-\<2.0, Gr4: \<1.0. Calcium (L) Gr 1: \<LLN to 8.0; Gr2: 7.0 - 8.0; Gr3: 6.0-7.0; Gr 4: \<6.0 mg/dL; calcium (H) Gr1:\>ULN - 11.5, Gr2:\>11.5 - 12.5, Gr3: 12.5 - 13.5, Gr4: \>13.5.
Trial Locations
- Locations (11)
University Of Maryland
🇺🇸Baltimore, Maryland, United States
Investigative Clinical Research Of Indiana, Llc
🇺🇸Indianapolis, Indiana, United States
Tennessee Oncology, Pllc
🇺🇸Nashville, Tennessee, United States
The University Of Texas M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Va Puget Sound Health Care System
🇺🇸Seattle, Washington, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Winship Cancer Institute, Emory University
🇺🇸Atlanta, Georgia, United States
University Of Iowa Hospitals And Clinics
🇺🇸Iowa City, Iowa, United States
Washington University School Of Medicine
🇺🇸Saint Louis, Missouri, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States