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Safety Study of IL-21/Ipilimumab Combination in the Treatment of Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01489059
First received: December 7, 2011
Last updated: August 28, 2014
Last verified: August 2014
  Purpose

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


Condition Intervention Phase
Melanoma
Biological: BMS-982470 (recombinant interleukin-21)
Biological: Ipilimumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    Based on the dose-limiting toxicity (DLT) rate

  • Part 2 (Cohort Escalation): Safety and tolerability of the MTD dose for each of the schedules [ Time Frame: 84 days on treatment ] [ Designated as safety issue: Yes ]
    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:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Trough observed serum concentration (Cmin) of BMS-982470 and Ipilimumab [ Time Frame: 1 time point each 3-week Cycle ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Incidence of BMS-984270 and Ipilimumab Anti-Drug Antibodies [ Time Frame: Up to 6 months following last dose ] [ Designated as safety issue: No ]

Enrollment: 42
Study Start Date: December 2011
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 - Arm 1: BMS-982470 (Daily x 5) + Ipilimumab
Dose Escalation
Biological: BMS-982470 (recombinant interleukin-21)
Solution, Intravenous, 10,30,50 μg/kg, daily for 5 days every 3 weeks (daily x 5), 16-20 weeks depending on response
Biological: Ipilimumab
Solution, Intravenous, 1,3,10 mg/kg, every 3 weeks, 16-20 weeks depending on response
Other Name: Yervoy®
Experimental: Part 1 - Arm 2: BMS-982470 (Weekly) + Ipilimumab
Dose Escalation
Biological: BMS-982470 (recombinant interleukin-21)
Solution, Intravenous, 30,100,150 μg/kg, weekly, 16-20 weeks depending on response
Biological: Ipilimumab
Solution, Intravenous, 1,3,10 mg/kg, every 3 weeks, 16-20 weeks depending on response
Other Name: Yervoy®
Experimental: Part 2 - Arm 1: BMS-982470 (Daily x 5) + Ipilimumab
Cohort Expansion
Biological: BMS-982470 (recombinant interleukin-21)
Solution, Intravenous, Maximum tolerated dose from Part 1, daily for 5 days every 3 weeks (daily x 5), 12-16 weeks depending on response
Biological: Ipilimumab
Solution, Intravenous, Maximum tolerated dose from Part 1, every 3 weeks, 12-16 weeks depending on response
Other Name: Yervoy®
Experimental: Part 2 - Arm 2: BMS-982470 (Weekly) + Ipilimumab
Cohort Expansion
Biological: BMS-982470 (recombinant interleukin-21)
Solution, Intravenous, Maximum tolerated dose from Part 1, Weekly, 12-16 weeks depending on response
Biological: Ipilimumab
Solution, Intravenous, Maximum tolerated dose from Part 1, every 3 weeks, 12-16 weeks depending on response
Other Name: Yervoy®
Active Comparator: Part 2 - Arm 3: Ipilimumab monotherapy
Cohort Expansion
Biological: Ipilimumab
Solution, Intravenous, 3mg/kg, Every 3 weeks, 12-16 weeks depending on response
Other Name: Yervoy®

Detailed Description:

Allocation: Part 1 Dose Escalation Phase: Non-randomized; Part 2 Cohort Expansion Phase: Randomized

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01489059

Locations
United States, Arizona
Oncology Research Associates, Pllc D/B/A
Scottsdale, Arizona, United States, 85258
United States, California
Ucla Hematology/Oncology.
Los Angeles, California, United States, 90095
United States, Florida
H. Lee Moffitt Cancer Center & Research Inst, Inc
Tampa, Florida, United States, 33612
United States, Indiana
Indiana University Health Melvin And Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Kentucky
University Of Louisville Medical Center, Inc., Dba
Louisville, Kentucky, United States, 40202
United States, Oregon
Portland Providence Medical Center
Portland, Oregon, United States, 97213
United States, Texas
Md Anderson Can Cnt
Houston, Texas, United States, 77030
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Puerto Rico
Local Institution
San Juan, Puerto Rico, 00927
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01489059     History of Changes
Other Study ID Numbers: CA220-007
Study First Received: December 7, 2011
Last Updated: August 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Antibodies, Monoclonal
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014