vaccine therapy with or without sargramostim in treating patients with high-risk or metastatic melanoma

Conditions: Melanoma (Skin)

Summary: rationale: vaccines made from peptides may make the body build an immune response to kill tumor cells. colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood. combining vaccine therapy with sargramostim may kill more tumor cells. purpose: randomized phase i trial to study the effectiveness of vaccine therapy with or without sargramostim in treating patients who have metastatic melanoma.

objectives: * compare the safety of melanoma peptide vaccine with or without sargramostim (gm-csf) in patients with high-risk or metastatic melanoma. * compare changes in peptide-specific cellular and humoral immunologic profiles in patients treated with these regimens. * compare tumor response in patients treated with these regimens. outline: this is a randomized, open-label study. patients are randomized to 1 of 2 treatment arms. * arm i: patients receive melanoma peptide vaccine comprising tyrosinase leader injected at 2 separate sites, melan-a ela injected at another site, ny-eso-1a and ny-eso-1b combined and injected at one site, and mage-10.a2 injected at another site, intradermally once weekly on weeks 1-6. * arm ii: patients receive vaccine as in arm i. patients also receive sargramostim (gm-csf) subcutaneously daily beginning 2 days before each vaccination and continuing for 5 days. treatment in both arms continues through week 6 in the absence of disease progression or unacceptable toxicity. patients are followed at 2 weeks. projected accrual: a total of 20 patients (10 per treatment arm) will be accrued for this study within 18 months.

Eligibility criteria:
disease characteristics: * histologically confirmed high-risk stage iii or iv melanoma * stage iii disease less than 6 months after surgical resection * completed prior interferon alfa therapy or * progressive disease or major adverse events during prior interferon alfa therapy * stage iii disease at least 6 months after surgical resection * declined, failed, or completed prior standard therapy * stage iv disease * declined, failed, or completed prior standard therapy * hla-a2 positive * no cns metastases unless treated and stable patient characteristics: age: * 18 and over performance status: * karnofsky 80-100% life expectancy: * at least 4 months hematopoietic: * neutrophil count at least 1,500/mm3 * lymphocyte count at least 500/mm3 * platelet count at least 100,000/mm3 * hemoglobin at least 9.0 g/dl (10.0 g/dl if less than 50 kg) * no bleeding disorder hepatic: * bilirubin no greater than 2.0 mg/dl * no hepatitis b or c positivity renal: * creatinine no greater than 1.8 mg/dl cardiovascular: * no new york heart association class iii or iv heart disease other: * hiv negative * no other serious illness * no serious infection requiring antibiotics * no history of immunodeficiency disease or autoimmune disease * no psychiatric or addictive disorder that would preclude study * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception prior concurrent therapy: biologic therapy: * see disease characteristics * no prior bone marrow or stem cell transplantation * at least 4 weeks since prior immunotherapy or biologic therapy * no other concurrent immunotherapy or biologic therapy chemotherapy: * at least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) * no concurrent chemotherapy endocrine therapy: * no concurrent systemic corticosteroids * no concurrent steroids except topical or inhalational steroids * concurrent hormonal therapy allowed radiotherapy: * at least 4 weeks since prior radiotherapy surgery: * see disease characteristics * at least 4 weeks since prior surgery other: * at least 4 weeks since prior investigational agents * concurrent noncytotoxic anticancer therapy allowed * no concurrent immunosuppressive therapy * no concurrent antihistamines * no concurrent non-steroidal anti-inflammatory drugs except in low doses for prevention of an acute cardiovascular event or pain control

Keywords: stage iii melanoma stage iv melanoma recurrent melanoma