Clinical trial NCT01489059: Safety Study of IL-21/Ipilimumab Combination in the Treatment of Melanoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2011-12-09
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility 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

Primary outcomes:
measure: Part1 (Dose Escalation): The Maximum tolerated dose (MTD) of BMS-982470 using 2 distinct schedules when administered in combination with Ipilimumab
timeFrame: Within the first 63 days
measure: Part 2 (Cohort Escalation): Safety and tolerability of the MTD dose for each of the schedules
timeFrame: 84 days on treatment
Secondary outcomes:
measure: Efficacy of BMS-982470 in combination with Ipilimumab as measured by objective response
timeFrame: Baseline (Day 1), End of Treatment (EOT) [3 weeks after last dose of Ipilimumab], 3 and 6 months Follow-up
measure: Area under the serum concentration-time curve from time zero to the last quantifiable concentration [AUC(0-T)] of BMS-982470 and Ipilimumab
timeFrame: 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3
measure: Area under the serum concentration-time curve in one dosing interval [AUC(TAU)] of BMS-982470 and Ipilimumab
timeFrame: 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3
measure: Area under the serum concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-982470 and Ipilimumab
timeFrame: 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3
measure: The maximum observed serum concentration (Cmax) of BMS-982470 and Ipilimumab
timeFrame: 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3
measure: Trough observed serum concentration (Cmin) of BMS-982470 and Ipilimumab
timeFrame: 1 time point each 3-week Cycle
measure: The time of maximum observed serum concentration (Tmax) of BMS-982470 and Ipilimumab
timeFrame: 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3
measure: Serum half-life (T-HALF) of BMS-982470 and Ipilimumab
timeFrame: 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3
measure: Apparent total body clearance (CLT) of BMS-982470 and Ipilimumab
timeFrame: 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3
measure: Apparent volume of distribution at steady state (Vss) of BMS-982470 and Ipilimumab
timeFrame: 20 time points during Lead-In Cycle; Up to 11 time points during Cycle 3
measure: Incidence of BMS-984270 and Ipilimumab Anti-Drug Antibodies
timeFrame: Up to 6 months following last dose
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Oncology Research Associates, Pllc D/B/A
state: Arizona
city: Los Angeles
country: United States
facility: Ucla Hematology/Oncology.
state: California
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Inst, Inc
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Health Melvin And Bren Simon Cancer Center
state: Indiana
city: Louisville
country: United States
facility: University Of Louisville Medical Center, Inc., Dba
state: Kentucky
city: Portland
country: United States
facility: Portland Providence Medical Center
state: Oregon
city: Houston
country: United States
facility: Md Anderson Can Cnt
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: San Juan
country: Puerto Rico
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: