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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 35
- 试验地点
- 11
- 主要终点
- Geometric Mean Maximum Observed Serum Concentration (Cmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
研究概览
简要总结
The purpose of the study is to assess the concentration of Elotuzumab in Myeloma patients with very low kidney function including patients on dialysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Arm 1: Lenalidomide + Dexamethasone +Elotuzumab
Severe Renal Impairment
干预措施: Lenalidomide (Drug)
Arm 1: Lenalidomide + Dexamethasone +Elotuzumab
Severe Renal Impairment
干预措施: Dexamethasone (Drug)
Arm 1: Lenalidomide + Dexamethasone +Elotuzumab
Severe Renal Impairment
干预措施: Elotuzumab (BMS-901608; HuLuc63) (Biological)
Arm 2: Lenalidomide + Dexamethasone +Elotuzumab
End-stage renal disease
干预措施: Lenalidomide (Drug)
Arm 2: Lenalidomide + Dexamethasone +Elotuzumab
End-stage renal disease
干预措施: Dexamethasone (Drug)
Arm 2: Lenalidomide + Dexamethasone +Elotuzumab
End-stage renal disease
干预措施: Elotuzumab (BMS-901608; HuLuc63) (Biological)
Arm 3: Lenalidomide + Dexamethasone +Elotuzumab
Normal renal function
干预措施: Lenalidomide (Drug)
Arm 3: Lenalidomide + Dexamethasone +Elotuzumab
Normal renal function
干预措施: Dexamethasone (Drug)
Arm 3: Lenalidomide + Dexamethasone +Elotuzumab
Normal renal function
干预措施: Elotuzumab (BMS-901608; HuLuc63) (Biological)
结局指标
主要结局
Geometric Mean Maximum Observed Serum Concentration (Cmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
时间窗: 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
时间窗: 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
次要结局
- 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))