HD IL-2 + Ipilimumab in Patients With Metastatic Melanoma

Phase 4

Terminated

Brief Summary: 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: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Treatment Arm 1	High Dose Interleukin-2	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	High Dose Interleukin-2	Patients will receive one course (four doses) of ipilimumab followed by two courses (four cycles) of HD IL-2.
Treatment Arm 2	Ipilimumab	Patients will receive one course (four doses) of ipilimumab followed by two courses (four cycles) of HD IL-2.
Treatment Arm 1	Ipilimumab	Patients will receive two courses (four cycles) of High Dose Interleukin-2 (HD IL-2) followed by one course (four doses) of ipilimumab.

Primary Outcome Measures

Name	Time	Method
Estimated One-year OS in the Evaluable Population in 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.	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.

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival	5-11 weeks, 13-19 Weeks, 24-30 weeks and 1 year	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.

Locations (12): Moores UCSD Cancer Center
🇺🇸
La Jolla, California, United States
MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Columbia University Medical Center, Herbert Irving Comprehensive Cancer Center
🇺🇸
New York, New York, United States
The University of Arizona Cancer Center
🇺🇸
Tucson, Arizona, United States
MSMC Research Program
🇺🇸
Miami Beach, Florida, United States
Duke University Health System
🇺🇸
Durham, North Carolina, United States
University of Iowa Hospitals & Clinics
🇺🇸
Iowa City, Iowa, United States
Johns Hopkins Medicine
🇺🇸
Lutherville, Maryland, United States
Nebraska Cancer Specialists, Midwest Cancer Center - Legacy
🇺🇸
Omaha, Nebraska, United States
The Christ Hospital
🇺🇸
Cincinnati, Ohio, United States
Oncology Specialists, SC
🇺🇸
Park Ridge, Illinois, United States
Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States