Safety Study of IL-21/Ipilimumab Combination in the Treatment of Melanoma
- Conditions
- Melanoma
- Interventions
- Biological: BMS-982470 (recombinant interleukin-21)Biological: Ipilimumab
- Registration Number
- NCT01489059
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to determine whether the combination of interleukin-21 (IL-21) and Ipilimumab in subjects with melanoma is safe, and provide preliminary information on the clinical benefits of the combination compared with Ipilimumab alone
- Detailed Description
Allocation: Part 1 Dose Escalation Phase: Non-randomized; Part 2 Cohort Expansion Phase: Randomized
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 42
- Unresectable Stage III or Stage IV melanoma
- Part 1 Dose Escalation: Prior melanoma treatment allowed except for the following: ipilimumab, BMS-982470 (rIL-21), anti-Programmed Death-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), anti-PD-L2 or anti-CD137
- Part 2 Cohort expansion: Prior treatment for melanoma is not allowed, except for adjuvant therapy with interferon alpha or melanoma vaccines which are permitted
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI)
- Normal liver function tests
- Part 1 Dose escalation: subjects with ≤ 2 brain metastases of stable size, ≥ 4 weeks post-radiation treatment, and off steroids are allowed
- Part 2 Cohort expansion: subjects with known or suspected brain metastases and uveal melanoma are excluded
- Autoimmune disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1 - Arm 1: BMS-982470 (Daily x 5) + Ipilimumab Ipilimumab Dose Escalation Part 2 - Arm 2: BMS-982470 (Weekly) + Ipilimumab BMS-982470 (recombinant interleukin-21) Cohort Expansion Part 1 - Arm 1: BMS-982470 (Daily x 5) + Ipilimumab BMS-982470 (recombinant interleukin-21) Dose Escalation Part 1 - Arm 2: BMS-982470 (Weekly) + Ipilimumab Ipilimumab Dose Escalation Part 1 - Arm 2: BMS-982470 (Weekly) + Ipilimumab BMS-982470 (recombinant interleukin-21) Dose Escalation Part 2 - Arm 1: BMS-982470 (Daily x 5) + Ipilimumab BMS-982470 (recombinant interleukin-21) Cohort Expansion Part 2 - Arm 1: BMS-982470 (Daily x 5) + Ipilimumab Ipilimumab Cohort Expansion Part 2 - Arm 2: BMS-982470 (Weekly) + Ipilimumab Ipilimumab Cohort Expansion Part 2 - Arm 3: Ipilimumab monotherapy Ipilimumab Cohort Expansion
- Primary Outcome Measures
Name Time Method Part1 (Dose Escalation): The Maximum tolerated dose (MTD) of BMS-982470 using 2 distinct schedules when administered in combination with Ipilimumab Within the first 63 days Based on the dose-limiting toxicity (DLT) rate
Part 2 (Cohort Escalation): Safety and tolerability of the MTD dose for each of the schedules 84 days on treatment Based on medical review of AE reports and the results of vital sign measurements, physical examinations, medical history, and clinical laboratory tests
- Secondary Outcome Measures
Name Time Method Area under the serum concentration-time curve from time zero to the last quantifiable concentration [AUC(0-T)] of BMS-982470 and Ipilimumab 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3 Area under the serum concentration-time curve in one dosing interval [AUC(TAU)] of BMS-982470 and Ipilimumab 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3 Area under the serum concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-982470 and Ipilimumab 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3 The maximum observed serum concentration (Cmax) of BMS-982470 and Ipilimumab 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3 Efficacy of BMS-982470 in combination with Ipilimumab as measured by objective response Baseline (Day 1), End of Treatment (EOT) [3 weeks after last dose of Ipilimumab], 3 and 6 months Follow-up Trough observed serum concentration (Cmin) of BMS-982470 and Ipilimumab 1 time point each 3-week Cycle The time of maximum observed serum concentration (Tmax) of BMS-982470 and Ipilimumab 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3 Serum half-life (T-HALF) of BMS-982470 and Ipilimumab 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3 Apparent total body clearance (CLT) of BMS-982470 and Ipilimumab 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3 Apparent volume of distribution at steady state (Vss) of BMS-982470 and Ipilimumab 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3 Incidence of BMS-984270 and Ipilimumab Anti-Drug Antibodies Up to 6 months following last dose
Trial Locations
- Locations (9)
Oncology Research Associates, Pllc D/B/A
🇺🇸Scottsdale, Arizona, United States
Ucla Hematology/Oncology.
🇺🇸Los Angeles, California, United States
Indiana University Health Melvin And Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
University Of Louisville Medical Center, Inc., Dba
🇺🇸Louisville, Kentucky, United States
Portland Providence Medical Center
🇺🇸Portland, Oregon, United States
H. Lee Moffitt Cancer Center & Research Inst, Inc
🇺🇸Tampa, Florida, United States
Md Anderson Can Cnt
🇺🇸Houston, Texas, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Local Institution
🇵🇷San Juan, Puerto Rico