A Companion Study for Patients Enrolled in Prior/Parent Ipilimumab Studies

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the continued use of ipilimumab in patients who had reinduction at the time of disease progression or to continue maintenance treatment. In addition, this study will continue to follow patients who have taken ipilimumab, but who are not eligible for maintenance or reinduction therapy.

Official Title
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A Multi-Center, Open-Label, Phase II Study of Ipilimumab (MDX-010 Extended-Treatment Monotherapy or Follow-up for Patients Previously Enrolled in Ipilimumab (MDX-010) Protocols.

Conditions
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Melanoma

Intervention / Treatment
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* Drug: 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 Key Inclusion Criteria Diagnosis of advanced melanoma Prior treatment in a prespecified prior/parent ipilimumab study Men and women 18 years of age and older First Reinduction: No unacceptable toxicity (except select reversible immune-related adverse events) requiring ipilimumab discontinuation Had experienced documented progressive disease after expanded clinical benefit Extended Maintenance Received ipilimumab at any dose in a parent study Achieved expanded clinical benefit at the time of entry to current study Follow-up: Received ipilimumab at any dose in a closing parent study Deemed ineligible for reinduction or extended maintenance treatment or refused treatment as reinduction or extended maintenance at the time of screening in the current study, but consented to follow-up Key Exclusion Criteria Prior treatment with a CD137 agonist or a cytotoxic T-lymphocyte antigen 4 inhibitor or agonist, other than ipilimumab Primary ocular or mucosal melanoma

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: First reinduction: Ipilimumab, 0.3 to 10 mg/kg<br>Participants who initially received ipilimumab, 0.3 mg/kg, in a parent study received ipilimumab, 10 mg/kg in the current study. Ipilimumab was administered as an individual open-label dose every 3 weeks for the first 10 weeks of reinduction for a total of 4 separate doses unless the patient experienced disease progression or withdrew consent. Participants had to wait 3 weeks from the last dose of ipilimumab in a parent study to the first dose of ipilimumab in the current study. | Drug: Ipilimumab<br>* Intravenous solution, 0.3, 3, or 10 mg/kg; 1 dose every 3 weeks or every 3 months until patient discontinuation<br>* Other names: MDX-010;|
| Experimental: First reinduction: Ipilimumab, 3 to 10 mg/kg<br>Participants who initially received ipilimumab, 3 mg/kg, in a parent study received ipilimumab, 10 mg/kg in the current study. Ipilimumab was administered as an individual open-label dose every 3 weeks for the first 10 weeks of reinduction for a total of 4 separate doses unless the patient experienced disease progression or withdrew consent. Participants had to wait 3 weeks from the last dose of ipilimumab in a parent study to the first dose of ipilimumab in the current study. | Drug: Ipilimumab<br>* Intravenous solution, 0.3, 3, or 10 mg/kg; 1 dose every 3 weeks or every 3 months until patient discontinuation<br>* Other names: MDX-010;|
| Experimental: First reinduction: Ipilimumab, 10 to 10 mg/kg<br>Participants who initially received ipilimumab, 10 mg/kg, in a parent study received ipilimumab, 10 mg/kg in the current study. Ipilimumab was administered as an individual open-label dose every 3 weeks for the first 10 weeks of reinduction for a total of 4 separate doses unless the patient experienced disease progression or withdrew consent. Participants had to wait 3 weeks from the last dose of ipilimumab in a parent study to the first dose of ipilimumab in the current study. | Drug: Ipilimumab<br>* Intravenous solution, 0.3, 3, or 10 mg/kg; 1 dose every 3 weeks or every 3 months until patient discontinuation<br>* Other names: MDX-010;|
| Experimental: Extended maintenance: Ipilimumab, 0.3 mg/kg<br>Participants who received ipilimumab, 0.3 mg/kg, in a parent study and who achieved extended clinical benefit received the same dose of ipilimumab (0.3 mg/kg) as maintenance in the current study. Maintenance dosing was administered every 12 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. | Drug: Ipilimumab<br>* Intravenous solution, 0.3, 3, or 10 mg/kg; 1 dose every 3 weeks or every 3 months until patient discontinuation<br>* Other names: MDX-010;|
| Experimental: Extended maintenance: Ipilimumab, 3 mg/kg<br>Participants who received ipilimumab, 3 mg/kg, in a parent study and who achieved extended clinical benefit received the same dose of ipilimumab (3 mg/kg) as maintenance in the current study. Maintenance dosing was administered every 12 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. | Drug: Ipilimumab<br>* Intravenous solution, 0.3, 3, or 10 mg/kg; 1 dose every 3 weeks or every 3 months until patient discontinuation<br>* Other names: MDX-010;|
| Experimental: Extended maintenance: Ipilimumab, 10 mg<br>Participants who received ipilimumab, 10 mg/kg, in a parent study and who achieved extended clinical benefit received the same dose of ipilimumab (10 mg/kg) as maintenance in the current study. Maintenance dosing was administered every 12 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. | Drug: Ipilimumab<br>* Intravenous solution, 0.3, 3, or 10 mg/kg; 1 dose every 3 weeks or every 3 months until patient discontinuation<br>* Other names: MDX-010;|
| No Intervention: Follow-up<br>Participants did not receive any additional study treatment in current study but continued follow-up for the collection of survival data. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With On-study Adverse Events (AEs), AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related AEs, Immune-related AEs (irAEs), and Death as Outcome | An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. An SAE is a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related is defined as having certain, probable, possible, or missing relationship to study drug. An IrAE is an AE characterized by a potential association with inflammation and considered by the investigator to be drug related. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. | Continuously from first dose to 70 days after last dose of study drug. For deaths, Day 1 of enrollment to 70 days after last dose of study drug. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was computed for all patients who entered this study and is defined as the time between the first dose of study therapy and death. If a patient has not died, OS was censored at the time of last contact. | From first dose of study drug in parent study to death or date of last censoring. | 
| Percentage of Participants Surviving at 1, 1.5, and 2 Years | Survival rate was defined as the time from first dose of study drug to 1, 1.5, and 2 years. | From first dose of study drug in parent study to up to 2 years after reinduction | 
| Number of Participants With On-study Immune-related Adverse Events (irAEs) | irAEs were defined as adverse events characterized by a potential association with inflammation and considered by the investigator as drug related. These prespecified terms were grouped into the following organ-specific subcategories: gastrointestinal, hepatic, skin, endocrine, neurologic, and other (includes blood, eye, immune system, investigations, infections, renal, and respiratory systems). Patients may have 1 or more events. | From first dose of study drug during reinduction to the earliest of 70 days after last dose or day before second reinduction first dose date | 
| Progression-free Survival (PFS) | PFS was defined as the time between the date of the baseline tumor assessment in this study and the date of progression or death, whichever occurred first. | From day of first reinduction in current study to date of progression or death, whichever occurred first. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ipilimumab, previously treated