vaccine therapy with or without interleukin-2 in treating patients with metastatic melanoma

Conditions: Melanoma (Skin)

Summary: rationale: vaccines may make the body build an immune response to kill tumor cells. interleukin-2 may stimulate a person's white blood cells to kill tumor cells. combining vaccine therapy with interleukin-2 may be an effective treatment for metastatic melanoma. purpose: phase ii trial to compare the effectiveness of vaccine therapy with or without interleukin-2 in treating patients who have metastatic melanoma that has not responded to previous therapy.

objectives: * compare the efficacy of gp100:209-217(210m) peptide and mart-1:26-35(27l) peptide administered with or without high-dose interleukin-2 (il-2) in patients with metastatic melanoma who are hla-a0201 positive. * determine the efficacy of these peptides in patients who cannot receive il-2. * compare the efficacy of il-2 with or without these peptides in patients who need immediate treatment with il-2. * determine the efficacy of mart-1:26-35(27l) peptide in patients who have received prior gp100 antigen. * compare the immunologic response experienced by patients who have received peptide, with or without il-2, as measured by changes in t-cell precursors from before to after treatment. * compare the toxic effects of these regimens in these patients. outline: this is a partially randomized study. patients are assigned to 1 of 4 treatment groups based on disease status and prior therapy. * group a (eligible to receive interleukin-2 (il-2) but not in immediate need; no prior immunization with gp100 or mart-1 antigen): patients are randomized to 1 of 2 treatment arms. * arm i: patients receive gp100 and mart-1 peptides emulsified in montanide isa-51 (isa-51) subcutaneously (sc) on day 1. (arm i closed as of 10/30/02). * arm ii: patients receive both peptides as in arm i on day 1 and high-dose il-2 iv over 15 minutes every 8 hours on days 2-5 (for up to 12 doses). (arm ii closed as of 10/30/02). * group b (ineligible to receive il-2 due to other debilitating disease): patients receive treatment as in group a, arm i. * group c (need immediate il-2 therapy due to extensive and rapid progression of disease): patients receive treatment as in group a, arm ii. (group c closed as of 10/30/02). * group d (prior immunization with gp100 antigen): patients receive modified mart-1:26-35(27l) peptide emulsified in isa-51 sc on day 1. treatment in all groups repeats every 3 weeks for 4 courses. patients who achieve a minor, mixed, or partial response may receive up to 12 additional courses. patients who achieve complete response receive 2 additional courses. patients are followed at 4-6 weeks. projected accrual: a total of 103 patients (15-25 for group a, arm i; 19-33 for group a, arm ii; and 15 each for groups b, c, and d) will be accrued for this study within 1 year.

Eligibility criteria:
disease characteristics: * histologically confirmed metastatic melanoma that has failed standard therapy * measurable disease * hla-a0201 positive patient characteristics: age: * 16 and over performance status: * ecog 0-2 life expectancy: * more than 3 months hematopoietic: * wbc at least 3,000/mm\^3 * platelet count at least 90,000/mm\^3 hepatic: * bilirubin no greater than 2.0 mg/dl (less than 3.0 mg/dl for patients with gilbert's syndrome) * ast/alt less than 3 times normal * hepatitis b surface antigen negative * no coagulation disorder renal: * creatinine no greater than 2.0 mg/dl cardiovascular: * no major cardiovascular disease * if cardiovascular disease or other debilitating symptoms present, may receive peptide emulsified with montanide isa-51 only pulmonary: * no major respiratory disease other: * not pregnant * fertile patients must use effective contraception * hiv negative * no active systemic infection * no autoimmune disease or immunodeficiency disease * no primary or secondary immunodeficiency prior concurrent therapy: biologic therapy: * at least 3 weeks since prior biologic therapy * no prior mart-1 antigen immunization chemotherapy: * at least 3 weeks since prior chemotherapy endocrine therapy: * at least 3 weeks since prior endocrine therapy * no concurrent steroid therapy radiotherapy: * at least 3 weeks since prior radiotherapy surgery: * prior surgery allowed

Keywords: stage iv melanoma recurrent melanoma