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

An Extended Dosing, Two-phase Study of MDX-010 as Monotherapy or in Combination With Tyrosinase/gp100/MART-1 Peptides Emulsified With Montanide ISA 51 VG in the Treatment of Subjects With Resected Stage III or Stage IV Melanoma

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Vaccines may make the body build an immune response to kill tumor cells. Combining the vaccines with Montanide ISA-51 may cause a stronger immune response and kill more tumor cells. Giving monoclonal antibody therapy together with vaccine therapy may be an effective treatment for stage III or stage IV melanoma.

PURPOSE: This phase II trial is studying how well giving monoclonal antibody therapy together with vaccine therapy works in treating patients with resected stage III or stage IV melanoma.

OBJECTIVES:

Primary

• Achieve at least a 40% autoimmune breakthrough event rate, as defined by the induction of grade 1, grade 2, or acceptable grade 3 drug-related autoimmune adverse events, in patients with resected stage III or IV melanoma treated with anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen emulsified in Montanide ISA-51.

Secondary

• Determine the incidence of drug-related autoimmune adverse events of any grade in patients treated with this regimen.
• Determine the time to disease relapse in patients treated with this regimen.
• Determine the 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 (MDX-010) IV over 90 minutes on day 1 of weeks 1, 9, 17, 25, 33, 41, and 53 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen emulsified in Montanide ISA-51 subcutaneously on day 1 of weeks 1, 3, 5, 7, 9, 11, 17, 21, 25, 33, 41, and 53.

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

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed melanoma

  • Stage III (≥ 3 positive lymph nodes) or stage IV disease
  • Mucosal or ocular melanoma allowed

• Completely resected within the past 6 months

• Patients with stage III resected melanoma rendered free of disease may have failed, been ineligible for, or refused prior treatment with interferon alfa

• Positive staining of tumor tissue for at least one of the following:

  • Antibody HMB-45 for gp100
  • Antibody HMB-45 for tyrosinase
  • Antibody HMB-45 for MART-1

• HLA-A*0201 positive by DNA allele-specific polymerase chain reaction assay

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 6 months

Hematopoietic

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

Hepatic

• AST ≤ 3 times upper limit of normal (ULN)*
• Bilirubin ≤ ULN* (< 3.0 mg/dL for patients with Gilbert's syndrome)
• No significant hepatic disease that would preclude study participation
• Hepatitis B surface antigen negative
• Hepatitis C antibody negative NOTE: * Unless attributable to disease

Renal

• Creatinine ≤ 2.0 mg/dL
• No significant renal disease that would preclude study participation

Cardiovascular

• No significant cardiac disease that would preclude study participation

Pulmonary

• No significant pulmonary disease that would preclude study participation

Immunologic

• No history of any of the following:

  • Inflammatory bowel disease or any other autoimmune bowel disease
  • Systemic lupus erythematosus
  • Rheumatoid arthritis
  • Autoimmune ocular disease

• No systemic hypersensitivity to Montanide ISA-51 or any vaccine component

• No active infection requiring therapy

• HIV negative

Other

• 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 significant gastrointestinal disease that would preclude study participation
• No significant psychiatric disease that would preclude study participation
• No other medical condition that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 4 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010)
• No prior gp100 antigen, MART-1 antigen, or tyrosinase peptide
• At least 4 weeks since prior immunotherapy for melanoma and recovered
• No other concurrent immunotherapy

Chemotherapy

• At least 4 weeks since prior chemotherapy for melanoma (6 weeks for nitrosoureas) and recovered
• No concurrent chemotherapy

Endocrine therapy

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

Radiotherapy

• At least 4 weeks since prior radiotherapy for melanoma and recovered

Surgery

• See Disease Characteristics
• At least 4 weeks since prior surgery for melanoma and recovered

Other

• No concurrent immunosuppressive agents (e.g., cyclosporine and its analog)
• Concurrent analgesic therapy allowed provided the dose is stable for the past 14 days