OBJECTIVES:

• Compare the immune responses of patients with HLA-A2 positive stage IV malignant melanoma treated with tyrosinase, MART-1, and gp100 antigens emulsified in Montanide ISA-51 with or without sargramostim (GM-CSF).
• Compare the safety and toxicity of these regimens in these patients.
• Collect preliminary data on therapeutic efficacy relating to parameters of immune function in these patients on these treatments.

OUTLINE: This is a randomized study. Patients are stratified according to dominant disease (visceral vs nonvisceral). Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive melanoma specific antigen peptides comprising tyrosinase, gp100, and MART 1:27-35 emulsified in Montanide ISA-51 subcutaneously. Vaccinations are administered at the site of the primary melanoma, and in the abdomen and the extremities (6 total injections per session) every 3 weeks for 6 months. Patients may then continue receiving vaccinations every 3 months for 1 year.
• Arms II and III: Patients receive vaccinations as in arm I, combined with two different concentrations of sargramostim (GM-CSF).

Patients are followed every 3 months until year 3.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically proven stage IV malignant melanoma that is refractory to standard treatment or for which no curative therapy exists
• Measurable disease
• HLA-A2 positive
• No known CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin greater than 9.0 g/dL

Hepatic:

• Alkaline phosphatase no greater than 3 times upper limit of normal (ULN)
• AST no greater than 3 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No New York Heart Association classification III or IV heart disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No concurrent seizure disorder
• No active concurrent psychiatric disorder requiring antipsychotic medication
• No concurrent uncontrolled infection
• No immune deficiency
• No other malignancy within the past 5 years except locally resected basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior tyrosinase peptide, gp100 antigen, or MART-1:27-35 antigen
• At least 4 weeks since prior biologic therapy or immunotherapy
• No other concurrent immunotherapy

Chemotherapy:

• At least 4 weeks since prior chemotherapy (at least 6 weeks since prior mitomycin or nitrosoureas) and recovered
• No concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy involving no more than 25% of bone marrow
• No concurrent radiotherapy

Surgery:

• Not specified