Vaccine Therapy and GM-CSF With or Without Low-Dose Aldesleukin in Treating Patients With Stage II, Stage III, or Stage IV Melanoma

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Aldesleukin may stimulate the white blood cells to kill tumor cells. Giving vaccine and different doses of GM-CSF mixed in incomplete Freund's adjuvant, with or without aldesleukin, may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and how well giving vaccine therapy together with GM-CSF, with or without low-dose aldesleukin, works in treating patients with stage II, stage III, or stage IV melanoma.

Detailed Description
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OBJECTIVES: Determine the safety and toxicity profile of peptide vaccine comprising MART-1 antigen, gp100 antigen, and survivin antigen in combination with sargramostim (GM-CSF) emulsified in incomplete Freund's adjuvant (IFA) with or without low-dose aldesleukin in patients with stage II-IV melanoma. Determine the immunologic effects of two different doses of GM-CSF coemulsified with melanoma peptides in IFA in these patients. Determine the immunological effects of low-dose aldesleukin therapy administered after peptide immunization in these patients. Collect preliminary data on the impact of the vaccine on clinical outcomes in these patients. OUTLINE: This is a pilot study. Patients are stratified according to disease stage (II vs III or IV). Patients are sequentially enrolled into 1 of 4 different dose schedules. Dose schedule 1: Patients receive gp100 antigen, MART-1 antigen, survivin antigen, and sargramostim (GM-CSF) emulsified in incomplete Freund's adjuvant (peptide vaccine) subcutaneously (SC) on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Dose schedule 2: Patients receive peptide vaccine as in group 1. Patients also receive low-dose aldesleukin SC twice daily on days 7-20. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Dose schedule 3: Patients receive peptide vaccine as in group 1 except with a higher dose of GM-CSF. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Dose schedule 4: Patients receive peptide vaccine as in group 1 except with a higher dose of GM-CSF. Patients also receive low-dose aldesleukin SC twice daily on days 7-20. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 5 patients receive treatment at subsequent dose schedule until the maximum tolerated dose schedule (MTDS) is determined. The MTDS is defined as the dose schedule preceding that at which 2 of 5 patients experience dose-limiting toxicity within the first course. After completion of study therapy, patients are followed every 3 months for up to 2 years. PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Official Title
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Melanoma Peptide Vaccines (MART1 Analog, gp100 and Survivin) With GM-CSF and Low-Dose IL-2 as Immune Adjuvants, A Pilot Study

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: MART-1 antigen
* Biological: IL-2
* Biological: gp100 antigen
* Biological: GM-CSF
* Biological: MART-1a peptide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed melanoma Stage II-IV disease Completely resected disease No known standard therapy that is potentially curative or proven capable of extending life expectancy exists HLA-A2 positive PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy ≥ 12 weeks ANC ≥ 1,500/mm³ Hemoglobin > 10 g/dL Platelet count ≥ 50,000/mm³ AST ≤ 3 times upper limit of normal (ULN) Alkaline phosphatase ≤ 3 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No uncontrolled or current infection No known allergy to vaccine or immunoadjuvant components No known immune deficiency PRIOR CONCURRENT THERAPY: No chemotherapy within the past 4 weeks and recovered No biologic therapy within the past 4 weeks No radiation therapy within the past 4 weeks

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MART1 Analog, gp100 and Survivin<br> | Biological: MART-1 antigen<br>* 1000 mcg; Day 1 of a 21 day cycle x 4<br>Biological: IL-2<br>* 0.5x10^6/m^2<br>* Other names: Interleukin-2, Proleukin®, aldesleukin;Biological: gp100 antigen<br>* 1000 mcg; Day 1 of a 21 day cycle x 4<br>Biological: GM-CSF<br>* 300mcg<br>* Other names: Leukine-Liquid, sargramostatin;Biological: MART-1a peptide<br>* 1000 mcg; Day 1 of a 21 day cycle x 4<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent changes in peptide vaccine-specific immune responses (tetramer frequencies) from pretreatment levels |  | 12 weeks | 
| Number and severity of hematologic and nonhematologic toxicities observed at each dose level |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delayed-type hypersensitivity positivity |  | 12 weeks | 
| Maximum percent change in CD4, CD8, CD14, CD19, and C20 levels from preimmunization levels |  | 12 weeks | 
| Time to treatment failure |  | 12 weeks | 
| Time to progression |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II melanoma, stage III melanoma, stage IV melanoma, recurrent melanoma