HD IL-2 + Ipilimumab in Patients With Metastatic Melanoma

Study Overview
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Brief Summary
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Phase IV, open-label, randomized, two-arm, multi-center study in patients with metastatic melanoma who are treatment naïve or have previously received a single non-immunologic therapy. Treatment Arm 1: HD IL-2 first, then ipilimumab Patients will receive two courses (four cycles) of High Dose Interleukin-2 (HD IL-2) followed by one course (four doses) of ipilimumab. Treatment Arm 2: Ipilimumab first then HD IL-2 Patients will receive one course (four doses) of ipilimumab followed by two courses (four cycles) of HD IL-2.

Detailed Description
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All patients will receive IL-2 at 600,000 international units per kilogram (kg) by intravenous bolus (IVB) every 8 hours for up to 14 planned doses with an additional cycle 14 days after the first. Ipilimumab 3mg/kg IV infusion Q3 weeks up to 4 doses4 doses A 3-6 week interval been the administration of the two drugs to allow for resolution of treatment-related toxicities. If corticosteroids were required during Ipilimumab administration, a 2-week period from discontinuation of steroid treatment to start of HD IL-2.

Official Title
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Open-Label, Randomized, Multi-Center Study Comparing the Sequence of High Dose Aldesleukin (Interleukin-2) and Ipilimumab (Yervoy) in Patients With Metastatic Melanoma

Conditions
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Metastatic Melanoma

Intervention / Treatment
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* Drug: High Dose Interleukin-2
* Drug: Ipilimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients 18 years or older Confirmed and measurable metastatic melanoma with at least one measurable lesion for evaluation of response Meets the requirements for HD IL-2 therapy per Institutional guidelines Meets the requirements for ipilimumab therapy per Institutional guidelines Treatment naïve or has received only one systemic therapy apart from adjuvant therapy. At least 4 weeks since last adjuvant therapy or other cancer treatment Willing and able to give informed consent and participate in study procedures as described in the 12PLK02 and 10PLK13 protocols. Patients consented for 12PLK02 will also be asked to participate in the 10PLK13 PROCLAIM registry study. Exclusion Criteria: Patients with known or suspected infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV) or other infectious hepatitis Pregnant, nursing or planning to become pregnant Untreated brain metastases. (Brain metastases that have been treated, which no longer require corticosteroid therapy and are without progression by MRI at least 6 weeks after definitive therapy are acceptable.) Received prior ipilimumab therapy (Prior Adjuvant Ipilimumab and Adjuvant Interferon are permitted with a minimum 4 week washout) Received prior HD IL-2 therapy. Received investigational drug within 30 days prior to study dosing. Patients may participate in non-interventional or observational clinical studies, including the 10PLK13 PROCLAIM registry study. Concomitant disease or condition that would interfere with the conduct of the study or that would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this study.

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: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: assess the sequenced use of HD IL2 and IPI in metastatic melanoma patients
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment Arm 1<br>Patients will receive two courses (four cycles) of High Dose Interleukin-2 (HD IL-2) followed by one course (four doses) of ipilimumab. | Drug: High Dose Interleukin-2<br> <br> * Other names: interleukin;Drug: Ipilimumab<br> <br> * Other names: anti-CTLA4;|
| Active Comparator: Treatment Arm 2<br>Patients will receive one course (four doses) of ipilimumab followed by two courses (four cycles) of HD IL-2. | Drug: High Dose Interleukin-2<br> <br> * Other names: interleukin;Drug: Ipilimumab<br> <br> * Other names: anti-CTLA4;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimated One-year OS in the Evaluable Population in Each Treatment Arm Separately | evaluable patients who received at least 50% of both research drugs and had their disease re-evaluated after baseline; defined in days for the start of the first treatment to death. percent of patients alive at 1 year; estimates were assessed using Kaplan-Meier method for the entire subject population for each treatment arm separately. | start of first treatment to date of death from any cause and patients alive at their last evaluation date were censored up to 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | duration of time (in Days) from start of the first treatment to the time of objective disease progression or death at one year. The immune-related response criteria (irRC) determined based on tumor burden calculated on the WHO method of multiplying the perpendicular dimensions of all lesions are summed to obtain the tumor burden. The total tumor burden + SPD (index lesions) + SPD (new measurable lesions) Based on CT scans and Physical exam at designated timepoints. CR- Disappearance of all known disease; PR>/equal to decrease; SD Neither CR or PD; PD 25%increase; new lesion. | 5-11 weeks, 13-19 Weeks, 24-30 weeks and 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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melanoma, metastatic, skin cancer, Stage IV, interleukin-2