monoclonal antibody therapy and vaccine therapy in treating patients with resected stage iii or stage iv melanoma

Conditions: Intraocular Melanoma; Melanoma (Skin)

Summary: 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.

Eligibility criteria:
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

Keywords: stage iii melanoma stage iv melanoma ciliary body and choroid melanoma, medium/large size extraocular extension melanoma iris melanoma recurrent melanoma recurrent intraocular melanoma metastatic intraocular melanoma