vaccine therapy in treating patients with melanoma

Conditions: Melanoma (Skin)

Summary: rationale: vaccines may make the body build an immune response to kill tumor cells. vaccine therapy may be an effective treatment for melanoma. purpose: randomized phase ii trial to study the effectiveness of three vaccine therapy regimens in treating patients who have melanoma.

objectives: * compare the immunologic activity of three different schedules of peptide immunization with gp100:209-217 (210m) or gp100:17-25 antigen and tyrosinase:368-376 (370d), tyrosinase:240-251 (244s), tyrosinase:206-214 (closed to accrual 11/05/01), or tyrosinase-related protein-1 (orf3):1-9 peptide (closed to accrual 11/05/01) emulsified in montanide isa-51 in patients with melanoma at high risk for recurrence. * compare the response rate to treatment with interleukin-2 (il-2) after being immunized with this regimen with the usual response rate to il-2 in this patient population. * determine whether an exploratory cohort of hla-a2-positive patients demonstrate immunologic activity to immunization with 2 peptides emulsified together. outline: this is a randomized study. patients are stratified according to hla type (a0201 vs a1 vs a3 vs a24 vs a31). (hla-a24 and hla-a31 closed to accrual 11/05/01). patients are randomized to 1 of 3 treatment arms and are given an assigned vaccine, which is emulsified in montanide isa-51. * hla typing: * hla-a2: gp100:209-217 (210m) and tyrosinase:368-376 (370d) * hla-a1: tyrosinase:240-251 (244s) * hla-a3: gp100:17-25 * hla-a24: tyrosinase:206-214 (closed to accrual 11/05/01) * hla-a31: tyrosinase-related protein-1 (orf3):1-9 (closed to accrual 11/05/01) * arm i: patients receive assigned vaccine subcutaneously (sc) weekly for 10 weeks followed by 3 weeks of no treatment. * arm ii: patients receive assigned vaccine sc on days 1, 22, 43, and 64. * arm iii: patients receive assigned vaccine sc on days 1-4, 22-25, 43-46, and 64-67. treatment in all arms repeats every 13 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. after the completion of the randomized arms of hla-a2 patients, additional hla-a2 patients receive immunization with gp100:209-217 (210m) and tyrosinase:368-376 (370d) emulsified in montanide isa-51 sc once every 3 weeks for 4 courses. patients with progressive disease may receive interleukin-2 iv over 15 minutes every 8 hours for up to 4 days. treatment repeats every 10-14 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. patients with stable disease or mixed or partial response to treatment may receive additional courses every 2 months. patients are followed at 6 months. projected accrual: a total of 324 patients (19-33 per arm for the hla-a0201 stratum, 13-16 per arm for the other 4 strata, and 33 per the additional hla-a2 cohort) will be accrued for this study within 2 years. (hla-a24 and hla-a31 closed to accrual 11/05/01).

Eligibility criteria:
disease characteristics: * diagnosis of melanoma, including one of the following characteristics: * lesions at least 1.5 mm in thickness * at least 1 positive lymph node * ulcerated lesion * local recurrence * metastatic lesions completely resected within the past 6 months * clinically disease free within the past 6 weeks * hla-a1, a3, a24, a31, or 0201 positive (hla-a24 and hla-a31 closed to accrual 11/05/01) * 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 (3.0 mg/dl in gilbert's syndrome) * ast and alt less than 3 times normal * hepatitis b surface antigen negative renal: * creatinine no greater than 2.0 mg/dl cardiovascular: * for interleukin-2 (il-2) therapy: * no cardiac ischemia, myocardial infarction, or cardiac arrhythmias * stress cardiac test required if abnormal ekg, symptoms of cardiac ischemia or arrhythmia, or older than 50 years pulmonary: * for il-2 therapy: * no obstructive or restrictive pulmonary disease * fev_1 greater than 60% predicted if prolonged history of cigarette smoking or symptoms of respiratory dysfunction other: * not pregnant * negative pregnancy test * fertile patients must use effective contraception * hiv negative * no active systemic infections, autoimmune disease, or active primary or secondary immunodeficiency prior concurrent therapy: biologic therapy: * at least 3 weeks since prior systemic biologic therapy for melanoma * no prior gp100 antigen or tyrosinase or trp-1 peptide * no other concurrent systemic biologic therapy for melanoma chemotherapy: * at least 3 weeks since prior systemic chemotherapy and recovered * no concurrent systemic chemotherapy for melanoma endocrine therapy: * at least 3 weeks since prior systemic endocrine therapy for melanoma * no concurrent systemic steroid therapy radiotherapy: * at least 3 weeks since prior systemic radiotherapy and recovered * no concurrent systemic radiotherapy for melanoma surgery: * see disease characteristics

Keywords: stage i melanoma stage ii melanoma stage iii melanoma stage iv melanoma recurrent melanoma