Phase 2 Study of Ipilimumab in Children and Adolescents (12 to < 18 Years) With Previously Treated or Untreated, Unresectable Stage III or Stage lV Malignant Melanoma

Study Overview
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Brief Summary
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The purpose of the study is to comply with the Pediatric Investigation Plan requirements of Ipilimumab

Official Title
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Phase 2 Study of Ipilimumab in Children and Adolescents (12 to < 18 Years) With Previously Treated or Untreated, Unresectable Stage III or Stage IV Malignant Melanoma

Conditions
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Malignant Melanoma

Intervention / Treatment
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* Biological: Ipilimumab


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: 12 < 18 years of age Previously treated or untreated, unresectable Stage III or Stage IV malignant melanoma Karnofsky Performance Status (KPS) or Lansky Score ≥ 50 Exclusion Criteria: Primary Ocular Melanoma Prior therapy with a Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) or Programmed death- 1 (PD-1) antagonist, or Programmed cell death- ligand 1 (PD-L1) or CD137 agonists Symptomatic brain metastases History of autoimmune diseases

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ipilimumab 3 mg/kg<br>Ipilimumab (3 mg/kg) was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles. | Biological: Ipilimumab<br> <br> * Other names: BMS- 734016;|
| Experimental: Ipilimumab 10 mg/kg<br>Ipilimumab (10 mg/kg) was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles. | Biological: Ipilimumab<br> <br> * Other names: BMS- 734016;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) Rate at 1 Year | Overall Survival (OS) was defined as the time from the start of ipilimumab treatment date to death due to any cause. If a participant had not died, the participant was censored at the time of last contact (last known alive date). OS rates at 1 year were calculated from both Kaplan-Meier estimates and the proportion of participants alive at 1 year following start of treatment. | 1 year following start of treatment (Assessed up to June 2016, approximately 38 months) | 
| Percentage of Participants With Severe Immune-Mediated Adverse Reactions (imARs) | The percentage of participants with severe Immune-mediated Adverse Reactions (imARs) was determined by dividing the number of participants with grade 3 or worse imARs by the total number of treated participants and expressing this number as a percentage. imARs were AEs determined by the investigator to have an immune-mediated etiology, including inflammatory events associated with ipilimumab treatment. | From first dose to 90 days after last dose (Assessed up to June 2016, approximately 38 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) | Disease control rate was defined as the percentage of all treated participants with a best overall response of Complete Response (CR), Partial Response (PR), or Stable disease (SD), based on the investigator's assessment per mWHO Criteria. CR= Complete disappearance of all non-index lesions. PR= Decrease, relative to baseline, of 50% or greater in the sum of the products of the two largest perpendicular diameters of all index lesions. SD= Does not meet criteria for complete or partial response, in the absence of progressive disease. PD= At least 25% increase in the sum of the products of all index lesions (taking as reference the smallest sum recorded at or following baseline) and/or the appearance of any new lesion(s). | From Day 1 of first subject, first treatment to Day 365 of last subject, first treatment (approximately 36 months) | 
| Progression Free Survival | Progression-Free Survival was defined as the time from the start of ipilimumab treatment to disease progression or death, whichever occurs first. A participant who died without reported progression was considered to have progressed on their date of death. For participants who remained alive and had not progressed, PFS was censored on the date of the last tumor assessment. | From date of first treatment until disease progression or death (Assessed up to June 2016, approximately 38 months) | 
| Best Overall Response Rate (BORR) | Best Overall Response Rate (BORR) was defined as the total number of participants with the best overall response of Complete Response (CR) or Partial Response (PR) divided by the total number of treated participants and expressed as a percentage. CR= Complete disappearance of all non-index lesions. PR= Decrease, relative to baseline, of 50% or greater in the sum of the products of the two largest perpendicular diameters of all index lesions. SD= Does not meet criteria for complete or partial response, in the absence of progressive disease. PD= At least 25% increase in the sum of the products of all index lesions (taking as reference the smallest sum recorded at or following baseline) and/or the appearance of any new lesion(s). | From Day 1 of first subject, first treatment to Day 365 of last subject, first treatment (approximately 36 months) | 
| Overall Survival Time | Overall Survival time was defined as the time from the start of ipilimumab treatment date to date of death due to any cause. Participants who had not died were censored at the time of last contact (last known alive date). | From date of first treatment to date of death (Assessed up to June 2016, approximately 38 months) |