Vaccine Therapy and Monoclonal Antibody Therapy in Treating Patients With Stage IV Melanoma

An Open-label Study Of MDX-010 In Combination With gp100 Peptides Emulsified With Montanide ISA 51 In The Treatment Of Patients With Stage IV Melanoma

RATIONALE: Vaccines made from peptides may make the body build an immune response to kill tumor cells. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining vaccine therapy with a monoclonal antibody may cause a stronger immune response and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining vaccine therapy with monoclonal antibody therapy in treating patients who have stage IV melanoma.

OBJECTIVES:

• Determine the clinical response in patients with stage IV melanoma when treated with anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody combined with gp100:209-217 and gp100:280-288 peptides emulsified in Montanide ISA-51.
• Determine a safety and adverse event profile of this regimen in these patients.
• Determine improved immunologic response in patients treated with this regimen.

OUTLINE: This is an open-label study.

Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody IV over 90 minutes immediately followed by gp100:209-217 and gp100:280-288 peptides emulsified in Montanide ISA-51 subcutaneously on days 1, 22, 43, and 64. Treatment repeats every 12 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed at 3 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 68 patients will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed stage IV melanoma

  • Mucosal or ocular melanoma allowed

• Clinically evaluable disease

• HLA-A*0201 positive

PATIENT CHARACTERISTICS:

Age:

• 16 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• At least 6 months

Hematopoietic:

• WBC at least 2,500/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL
• Hematocrit at least 30%

Hepatic:

• AST no greater than 3 times upper limit of normal (ULN)
• Bilirubin no greater than ULN (less than 3.0 mg/dL in patients with Gilbert's syndrome)
• Hepatitis B surface antigen negative
• Hepatitis C antibody nonreactive

Renal:

• Creatinine less than 2.0 mg/dL

Immunologic:

• Antinuclear antibody negative
• Thyroglobulin antibody normal
• Rheumatoid factor normal
• HIV negative
• No prior autoimmune disease (including uveitis and autoimmune inflammatory eye disease)
• No active infection
• No hypersensitivity to Montanide ISA-51

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix
• No other underlying medical condition that would preclude study therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 3 weeks since prior immunotherapy for melanoma and recovered
• No prior gp100 peptides
• No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody

Chemotherapy:

• At least 3 weeks since prior chemotherapy for melanoma and recovered
• No concurrent chemotherapy

Endocrine therapy:

• At least 3 weeks since prior hormonal therapy for melanoma and recovered
• At least 4 weeks since prior systemic or topical corticosteroids
• No concurrent topical or systemic corticosteroids

Radiotherapy:

• At least 3 weeks since prior radiotherapy for melanoma and recovered

Surgery:

• Not specified

Other:

• No other concurrent immunosuppressive agents (e.g., cyclosporine and its analog)