OBJECTIVES:

• Compare the immunologic activity of immunization with MART-1:27-35, 27-35 (27L):MART-1, or MART-1:26-35 (27L) peptide or 27-35 (27L):MART-1 peptide combined with gp100:209-217 (210M) antigen peptide, in terms of immune response in HLA-A*0201-positive patients at high risk for recurrence of melanoma.
• Compare the response rate to treatment with interleukin-2 (IL-2) upon disease recurrence after immunization with the usual response rate to IL-2 in patients with metastatic melanoma.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive MART-1:27-35 peptide emulsified with Montanide ISA-51 (ISA-51) subcutaneously (SC) on day 1 every 3 weeks for a total of 4 doses (1 course).
• Arm II: Patients receive 27-35 (27L):MART-1 peptide emulsified with ISA-51 SC on day 1 every 3 weeks for a total of 4 doses (1 course).
• Arm III: Patients receive MART-1:26-35 (27L) peptide emulsified with ISA-51 SC on day 1 every 3 weeks for a total of 4 doses (1 course).
• Arm IV: Patients receive 27-35 (27L):MART-1 peptide and gp 100:209-217 (210M) antigen peptide emulsified with ISA-51 SC on day 1 every 3 weeks for a total of 4 doses (1 course).

In all arms, treatment continues in the absence of unacceptable toxicity or progressive disease. Patients with tumor recurrence during the first course with an easily resectable lesion undergo surgery to eradicate evidence of disease and continue with immunization. Patients with disease progression, other than the preceding, do not receive further peptide administration and are considered for interleukin-2 (IL-2) therapy.

• Interleukin-2 (IL-2) therapy: Patients receive IL-2 IV over 15 minutes every 8 hours for up to 4 days (maximum of 12 doses). Treatment repeats once after 10-14 days (1 course) in the absence of unacceptable toxicity. Patients with stable disease or a partial response are re-treated every 2 months. Patients with stable disease may receive up to 2 courses of re-treatment. Patients who continue to respond receive re-treatment as long as the disease is regressing. A maximum of 1 re-treatment is given after a complete response. After 4 courses of IL-2, patients who show no evidence of stable or responding disease are removed from the study.

Patients are followed every 3 months for 1 year and then every 6 months for 5 years or until disease progression.

PROJECTED ACCRUAL: A total of 76-132 patients (19-33 per treatment arm) will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Diagnosis of melanoma considered at high risk for recurrence with at least 1 of the following characteristics:
• Lesions at least 1.5 mm in thickness*
• At least 1 positive lymph node*
• Ulcerated lesions*
• Local recurrence*
• Completely resected metastatic melanoma NOTE: *Within 6 months of surgical resection
• HLA-A*0201 positive
• Must be clinically disease free (by radiologic studies within 6 weeks of study entry)
• No ocular or mucosal melanoma

PATIENT CHARACTERISTICS:

Age

• 16 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,000/mm^3
• Platelet count at least 90,000/mm^3

Hepatic

• Bilirubin no greater than 1.6 mg/dL (less than 3.0 mg/dL in patients with Gilbert's syndrome)
• AST/ALT less than 3 times normal
• Hepatitis B surface antigen negative

Renal

• Creatinine no greater than 2.0 mg/dL

Immunologic

• No active primary or secondary immunodeficiency
• No known hypersensitivity to any study agents
• No autoimmune disease
• No active systemic infection
• HIV negative

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 3 weeks since prior adjuvant immunotherapy (including interferon)
• At least 3 weeks since prior biologic therapy for metastatic disease
• No prior immunization with MART-1

Chemotherapy

• At least 3 weeks since prior chemotherapy for metastatic disease and recovered

Endocrine therapy

• No concurrent systemic steroid therapy

Radiotherapy

• Recovered from prior radiotherapy

Surgery

• See Disease Characteristics

Other

• At least 3 weeks since prior systemic anticancer therapy except surgery and recovered from toxic effects other than those which have no clinical implications (e.g., vitiligo and alopecia)
• No other concurrent systemic anticancer therapy