Safety Study of IL-21/Ipilimumab Combination in the Treatment of Melanoma
August 28, 2014 updated by: Bristol-Myers Squibb
A Phase I Dose Escalation Study of BMS-982470 (Recombinant Interleukin 21, rIL-21) in Combination With Ipilimumab in Subjects With Unresectable Stage III or Stage IV Melanoma
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
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Allocation: Part 1 Dose Escalation Phase: Non-randomized; Part 2 Cohort Expansion Phase: Randomized
Study Type
Interventional
Enrollment (Actual)
42
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
San Juan, Puerto Rico, 00927
- Local Institution
-
-
-
-
Arizona
-
Scottsdale, Arizona, United States, 85258
- Oncology Research Associates, Pllc D/B/A
-
-
California
-
Los Angeles, California, United States, 90095
- Ucla Hematology/Oncology.
-
-
Florida
-
Tampa, Florida, United States, 33612
- H. Lee Moffitt Cancer Center & Research Inst, Inc
-
-
Indiana
-
Indianapolis, Indiana, United States, 46202
- Indiana University Health Melvin and Bren Simon Cancer Center
-
-
Kentucky
-
Louisville, Kentucky, United States, 40202
- University Of Louisville Medical Center, Inc., Dba
-
-
Oregon
-
Portland, Oregon, United States, 97213
- Portland Providence Medical Center
-
-
Texas
-
Houston, Texas, United States, 77030
- Md Anderson Can Cnt
-
-
Washington
-
Seattle, Washington, United States, 98109
- Seattle Cancer Care Alliance
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Part 1 - Arm 1: BMS-982470 (Daily x 5) + Ipilimumab
Dose Escalation
|
Solution, Intravenous, 10,30,50 μg/kg, daily for 5 days every 3 weeks (daily x 5), 16-20 weeks depending on response
Solution, Intravenous, 30,100,150 μg/kg, weekly, 16-20 weeks depending on response
Solution, Intravenous, Maximum tolerated dose from Part 1, daily for 5 days every 3 weeks (daily x 5), 12-16 weeks depending on response
Solution, Intravenous, Maximum tolerated dose from Part 1, Weekly, 12-16 weeks depending on response
Solution, Intravenous, 1,3,10 mg/kg, every 3 weeks, 16-20 weeks depending on response
Other Names:
Solution, Intravenous, Maximum tolerated dose from Part 1, every 3 weeks, 12-16 weeks depending on response
Other Names:
Solution, Intravenous, 3mg/kg, Every 3 weeks, 12-16 weeks depending on response
Other Names:
|
|
Experimental: Part 1 - Arm 2: BMS-982470 (Weekly) + Ipilimumab
Dose Escalation
|
Solution, Intravenous, 10,30,50 μg/kg, daily for 5 days every 3 weeks (daily x 5), 16-20 weeks depending on response
Solution, Intravenous, 30,100,150 μg/kg, weekly, 16-20 weeks depending on response
Solution, Intravenous, Maximum tolerated dose from Part 1, daily for 5 days every 3 weeks (daily x 5), 12-16 weeks depending on response
Solution, Intravenous, Maximum tolerated dose from Part 1, Weekly, 12-16 weeks depending on response
Solution, Intravenous, 1,3,10 mg/kg, every 3 weeks, 16-20 weeks depending on response
Other Names:
Solution, Intravenous, Maximum tolerated dose from Part 1, every 3 weeks, 12-16 weeks depending on response
Other Names:
Solution, Intravenous, 3mg/kg, Every 3 weeks, 12-16 weeks depending on response
Other Names:
|
|
Experimental: Part 2 - Arm 1: BMS-982470 (Daily x 5) + Ipilimumab
Cohort Expansion
|
Solution, Intravenous, 10,30,50 μg/kg, daily for 5 days every 3 weeks (daily x 5), 16-20 weeks depending on response
Solution, Intravenous, 30,100,150 μg/kg, weekly, 16-20 weeks depending on response
Solution, Intravenous, Maximum tolerated dose from Part 1, daily for 5 days every 3 weeks (daily x 5), 12-16 weeks depending on response
Solution, Intravenous, Maximum tolerated dose from Part 1, Weekly, 12-16 weeks depending on response
Solution, Intravenous, 1,3,10 mg/kg, every 3 weeks, 16-20 weeks depending on response
Other Names:
Solution, Intravenous, Maximum tolerated dose from Part 1, every 3 weeks, 12-16 weeks depending on response
Other Names:
Solution, Intravenous, 3mg/kg, Every 3 weeks, 12-16 weeks depending on response
Other Names:
|
|
Experimental: Part 2 - Arm 2: BMS-982470 (Weekly) + Ipilimumab
Cohort Expansion
|
Solution, Intravenous, 10,30,50 μg/kg, daily for 5 days every 3 weeks (daily x 5), 16-20 weeks depending on response
Solution, Intravenous, 30,100,150 μg/kg, weekly, 16-20 weeks depending on response
Solution, Intravenous, Maximum tolerated dose from Part 1, daily for 5 days every 3 weeks (daily x 5), 12-16 weeks depending on response
Solution, Intravenous, Maximum tolerated dose from Part 1, Weekly, 12-16 weeks depending on response
Solution, Intravenous, 1,3,10 mg/kg, every 3 weeks, 16-20 weeks depending on response
Other Names:
Solution, Intravenous, Maximum tolerated dose from Part 1, every 3 weeks, 12-16 weeks depending on response
Other Names:
Solution, Intravenous, 3mg/kg, Every 3 weeks, 12-16 weeks depending on response
Other Names:
|
|
Active Comparator: Part 2 - Arm 3: Ipilimumab monotherapy
Cohort Expansion
|
Solution, Intravenous, 1,3,10 mg/kg, every 3 weeks, 16-20 weeks depending on response
Other Names:
Solution, Intravenous, Maximum tolerated dose from Part 1, every 3 weeks, 12-16 weeks depending on response
Other Names:
Solution, Intravenous, 3mg/kg, Every 3 weeks, 12-16 weeks depending on response
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Part1 (Dose Escalation): The Maximum tolerated dose (MTD) of BMS-982470 using 2 distinct schedules when administered in combination with Ipilimumab
Time Frame: Within the first 63 days
|
Based on the dose-limiting toxicity (DLT) rate
|
Within the first 63 days
|
|
Part 2 (Cohort Escalation): Safety and tolerability of the MTD dose for each of the schedules
Time Frame: 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
|
84 days on treatment
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Efficacy of BMS-982470 in combination with Ipilimumab as measured by objective response
Time Frame: Baseline (Day 1), End of Treatment (EOT) [3 weeks after last dose of Ipilimumab], 3 and 6 months Follow-up
|
Baseline (Day 1), End of Treatment (EOT) [3 weeks after last dose of Ipilimumab], 3 and 6 months Follow-up
|
|
Area under the serum concentration-time curve from time zero to the last quantifiable concentration [AUC(0-T)] of BMS-982470 and Ipilimumab
Time Frame: 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3
|
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
Time Frame: 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3
|
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
Time Frame: 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3
|
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
Time Frame: 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3
|
20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3
|
|
Trough observed serum concentration (Cmin) of BMS-982470 and Ipilimumab
Time Frame: 1 time point each 3-week Cycle
|
1 time point each 3-week Cycle
|
|
The time of maximum observed serum concentration (Tmax) of BMS-982470 and Ipilimumab
Time Frame: 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3
|
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
Time Frame: 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3
|
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
Time Frame: 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3
|
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
Time Frame: 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3
|
20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3
|
|
Incidence of BMS-984270 and Ipilimumab Anti-Drug Antibodies
Time Frame: Up to 6 months following last dose
|
Up to 6 months following last dose
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2011
Primary Completion (Actual)
June 1, 2014
Study Completion (Actual)
June 1, 2014
Study Registration Dates
First Submitted
December 7, 2011
First Submitted That Met QC Criteria
December 7, 2011
First Posted (Estimate)
December 9, 2011
Study Record Updates
Last Update Posted (Estimate)
August 29, 2014
Last Update Submitted That Met QC Criteria
August 28, 2014
Last Verified
August 1, 2014
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Melanoma
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Ipilimumab
Other Study ID Numbers
- CA220-007
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.