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

Melanoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01489059
• Other study ID #: CA220-007
• Status: Completed
• Phase: Phase 1
• First received: December 7, 2011
• Last updated: August 28, 2014
• Start date: December 2011
• Est. completion date: June 2014

Study information

• Verified date: August 2014
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma

Intervention

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
• BMS-982470 (recombinant interleukin-21)
Solution, Intravenous, 30,100,150 µg/kg, weekly, 16-20 weeks depending on response
• 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
• BMS-982470 (recombinant interleukin-21)
Solution, Intravenous, Maximum tolerated dose from Part 1, Weekly, 12-16 weeks depending on response
• Ipilimumab
Solution, Intravenous, 1,3,10 mg/kg, every 3 weeks, 16-20 weeks depending on response
• Ipilimumab
Solution, Intravenous, Maximum tolerated dose from Part 1, every 3 weeks, 12-16 weeks depending on response
• Ipilimumab
Solution, Intravenous, 3mg/kg, Every 3 weeks, 12-16 weeks depending on response

Locations

Country	Name	City	State
Puerto Rico	Local Institution	San Juan
United States	Md Anderson Can Cnt	Houston	Texas
United States	Indiana University Health Melvin And Bren Simon Cancer Center	Indianapolis	Indiana
United States	Ucla Hematology/Oncology.	Los Angeles	California
United States	University Of Louisville Medical Center, Inc., Dba	Louisville	Kentucky
United States	Portland Providence Medical Center	Portland	Oregon
United States	Oncology Research Associates, Pllc D/B/A	Scottsdale	Arizona
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	H. Lee Moffitt Cancer Center & Research Inst, Inc	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part1 (Dose Escalation): The Maximum tolerated dose (MTD) of BMS-982470 using 2 distinct schedules when administered in combination with Ipilimumab	Based on the dose-limiting toxicity (DLT) rate	Within the first 63 days	Yes
Primary	Part 2 (Cohort Escalation): Safety and tolerability of the MTD dose for each of the schedules	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Trough observed serum concentration (Cmin) of BMS-982470 and Ipilimumab		1 time point each 3-week Cycle	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Incidence of BMS-984270 and Ipilimumab Anti-Drug Antibodies		Up to 6 months following last dose	No

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