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

Primary Purpose

Melanoma

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

BMS-982470 (recombinant interleukin-21)

Ipilimumab

About this trial

This is an interventional treatment trial for Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Oncology Research Associates, Pllc D/B/A
Ucla Hematology/Oncology.
H. Lee Moffitt Cancer Center & Research Inst, Inc
Indiana University Health Melvin And Bren Simon Cancer Center
University Of Louisville Medical Center, Inc., Dba
Portland Providence Medical Center
Md Anderson Can Cnt
Seattle Cancer Care Alliance
Local Institution

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Active Comparator

Arm Label

Part 1 - Arm 1: BMS-982470 (Daily x 5) + Ipilimumab

Part 1 - Arm 2: BMS-982470 (Weekly) + Ipilimumab

Part 2 - Arm 1: BMS-982470 (Daily x 5) + Ipilimumab

Part 2 - Arm 2: BMS-982470 (Weekly) + Ipilimumab

Part 2 - Arm 3: Ipilimumab monotherapy

Arm Description

Dose Escalation

Cohort Expansion

Outcomes

Primary Outcome Measures

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

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

Secondary Outcome Measures

Efficacy of BMS-982470 in combination with Ipilimumab as measured by objective response

Area under the serum concentration-time curve from time zero to the last quantifiable concentration [AUC(0-T)] of BMS-982470 and Ipilimumab

Area under the serum concentration-time curve in one dosing interval [AUC(TAU)] of BMS-982470 and Ipilimumab

Area under the serum concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-982470 and Ipilimumab

The maximum observed serum concentration (Cmax) of BMS-982470 and Ipilimumab

Trough observed serum concentration (Cmin) of BMS-982470 and Ipilimumab

The time of maximum observed serum concentration (Tmax) of BMS-982470 and Ipilimumab

Serum half-life (T-HALF) of BMS-982470 and Ipilimumab

Apparent total body clearance (CLT) of BMS-982470 and Ipilimumab

Apparent volume of distribution at steady state (Vss) of BMS-982470 and Ipilimumab

Incidence of BMS-984270 and Ipilimumab Anti-Drug Antibodies

Full Information

NCT ID

NCT01489059

First Posted

December 7, 2011

Last Updated

August 28, 2014

Sponsor

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT01489059

Brief Title

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

2. Study Status

Record Verification Date

August 2014

Overall Recruitment Status

Completed

Study Start Date

December 2011 (undefined)

Primary Completion Date

June 2014 (Actual)

Study Completion Date

June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

42 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1 - Arm 1: BMS-982470 (Daily x 5) + Ipilimumab

Arm Type

Experimental

Arm Description

Dose Escalation

Arm Title

Part 1 - Arm 2: BMS-982470 (Weekly) + Ipilimumab

Arm Type

Experimental

Arm Description

Dose Escalation

Arm Title

Part 2 - Arm 1: BMS-982470 (Daily x 5) + Ipilimumab

Arm Type

Experimental

Arm Description

Cohort Expansion

Arm Title

Part 2 - Arm 2: BMS-982470 (Weekly) + Ipilimumab

Arm Type

Experimental

Arm Description

Cohort Expansion

Arm Title

Part 2 - Arm 3: Ipilimumab monotherapy

Arm Type

Active Comparator

Arm Description

Cohort Expansion

Intervention Type

Biological

Intervention Name(s)

BMS-982470 (recombinant interleukin-21)

Intervention Description

Solution, Intravenous, 10,30,50 μg/kg, daily for 5 days every 3 weeks (daily x 5), 16-20 weeks depending on response

Intervention Type

Biological

Intervention Name(s)

BMS-982470 (recombinant interleukin-21)

Intervention Description

Solution, Intravenous, 30,100,150 μg/kg, weekly, 16-20 weeks depending on response

Intervention Type

Biological

Intervention Name(s)

BMS-982470 (recombinant interleukin-21)

Intervention Description

Solution, Intravenous, Maximum tolerated dose from Part 1, daily for 5 days every 3 weeks (daily x 5), 12-16 weeks depending on response

Intervention Type

Biological

Intervention Name(s)

BMS-982470 (recombinant interleukin-21)

Intervention Description

Solution, Intravenous, Maximum tolerated dose from Part 1, Weekly, 12-16 weeks depending on response

Intervention Type

Biological

Intervention Name(s)

Ipilimumab

Other Intervention Name(s)

Yervoy®

Intervention Description

Solution, Intravenous, 1,3,10 mg/kg, every 3 weeks, 16-20 weeks depending on response

Intervention Type

Biological

Intervention Name(s)

Ipilimumab

Other Intervention Name(s)

Yervoy®

Intervention Description

Solution, Intravenous, Maximum tolerated dose from Part 1, every 3 weeks, 12-16 weeks depending on response

Intervention Type

Biological

Intervention Name(s)

Ipilimumab

Other Intervention Name(s)

Yervoy®

Intervention Description

Solution, Intravenous, 3mg/kg, Every 3 weeks, 12-16 weeks depending on response

Primary Outcome Measure Information:

Title

Part1 (Dose Escalation): The Maximum tolerated dose (MTD) of BMS-982470 using 2 distinct schedules when administered in combination with Ipilimumab

Description

Based on the dose-limiting toxicity (DLT) rate

Time Frame

Within the first 63 days

Title

Part 2 (Cohort Escalation): Safety and tolerability of the MTD dose for each of the schedules

Description

Based on medical review of AE reports and the results of vital sign measurements, physical examinations, medical history, and clinical laboratory tests

Time Frame

84 days on treatment

Secondary Outcome Measure Information:

Title

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

Title

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

Title

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

Title

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

Title

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

Title

Trough observed serum concentration (Cmin) of BMS-982470 and Ipilimumab

Time Frame

1 time point each 3-week Cycle

Title

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

Title

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

Title

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

Title

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

Title

Incidence of BMS-984270 and Ipilimumab Anti-Drug Antibodies

Time Frame

Up to 6 months following last dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bristol-Myers Squibb

Organizational Affiliation

Bristol-Myers Squibb

Official's Role

Study Director

Facility Information:

Facility Name

Oncology Research Associates, Pllc D/B/A

City

Scottsdale

State/Province

Arizona

ZIP/Postal Code

85258

Country

United States

Facility Name

Ucla Hematology/Oncology.

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

H. Lee Moffitt Cancer Center & Research Inst, Inc

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

Facility Name

Indiana University Health Melvin And Bren Simon Cancer Center

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

University Of Louisville Medical Center, Inc., Dba

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40202

Country

United States

Facility Name

Portland Providence Medical Center

City

Portland

State/Province

Oregon

ZIP/Postal Code

97213

Country

United States

Facility Name

Md Anderson Can Cnt

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Seattle Cancer Care Alliance

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109

Country

United States

Facility Name

Local Institution

City

San Juan

ZIP/Postal Code

00927

Country

Puerto Rico

12. IPD Sharing Statement

Links:

URL

http://www.bms.com/studyconnect/Pages/home.aspx

Description

BMS clinical trial educational resource

Learn more about this trial

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

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