Vaccine Therapy in Treating Patients With Recurrent Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

OBJECTIVES:

• Determine the safety of a peptide vaccine comprising MART-1:27-35 peptide, gp100:209-217 (210M) peptide, and tyrosinase peptide with sargramostim (GM-CSF) and CpG 7909 emulsified in incomplete Freund's adjuvant in patients with unresectable recurrent stage III or IV melanoma.
• Determine the efficacy of immunoadjuvants CpG 7909 and GM-CSF, in terms of a strong antigen-specific CD8+ T-cell response, in these patients.
• Determine the anti-pigmentary response to this regimen in these patients.
• Determine the anti-tumor response, in terms of objective tumor regression, progression-free survival, and overall survival, in patients treated with this regimen.

OUTLINE: This is a pilot study.

Patients receive peptide vaccine comprising MART-1:27-35 peptide, gp100:209-217 (210M) peptide, and tyrosinase peptide with sargramostim (GM-CSF) and CpG 7909 emulsified in incomplete Freund's adjuvant subcutaneously on days 1 and 15. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline, day 50-53, and day 91-94. Samples are examined by ELISPOT assay to measure lymphocyte immune response and by flow cytometry for biomarker quantification and T-cell response.

After completion of study treatment, patients are followed up periodically for at least 2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed melanoma meeting the following criteria:

• Unresectable recurrent disease
• Stage III or IV disease
• Cutaneous, ocular, or mucosal melanoma
• Measurable disease as defined by the RECIST criteria
• HLA-A2 positive
• Prior brain metastases allowed provided adequate surgical or radiologic treatment for brain disease

PATIENT CHARACTERISTICS:

• ECOG performance status 0 or 1
• WBC ≥ 3,000/mm³
• Lymphocytes ≥ 1,000/mm³
• Platelet count ≥ 100,000/mm³
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• AST and ALT ≤ 2.5 times ULN
• Lactic dehydrogenase ≤ 2.0 times ULN
• aPTT < 40 seconds
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception for ≥ 1 week before, during, and for ≥ 2 weeks after completion of study therapy
• No conditions of immunosuppression
• Negative titers for antinuclear antibody (≤ 1/80) and antidouble stranded DNA (≤ 1/10)
• No serious illnesses including, but not limited to, any of the following:

• Bleeding disorders
• Autoimmune diseases
• Severe obstructive or restrictive pulmonary diseases
• Active systemic infections
• Inflammatory bowel disorders
• No serious cardiovascular disease including, but not limited to, any of the following:

• Uncontrolled congestive heart failure
• Hypertension
• Cardiac ischemia
• Myocardial infarction,
• Severe cardiac arrhythmia
• HIV1 and 2 negative
• HTLV-1 negative
• Hepatitis B and C negative
• No significant psychiatric disease, medical intervention, or other condition that, in the opinion of the principal investigator, would limit study compliance
• No active infection within the past week, including unexplained fever (temperature > 38.1°C)

PRIOR CONCURRENT THERAPY:

• Fully recovered from prior major surgery
• More than 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas), hormonal therapy, radiotherapy, or biological therapy
• More than 1 week since prior antibiotics
• More than 28 days since prior investigational agent
• No prior vaccination with MART-1 (26-35, 27L), gp100 (209-217, 210M), and tyrosinase (368-376, 370D) peptides alone or in combination

• Patients with history of vaccination with peptides other than MART-1 (26-35, 27L), gp100 (209-217, 210M), and tyrosinase (368-376, 370D) peptides allowed
• More than 4 weeks since prior and no concurrent systemic immunosuppressive therapy, including steroids

• Patients on maintenance steroids given at physiologic doses because of adrenal insufficiency are eligible
• More than 2 weeks since prior and no concurrent treatment with systemic steroids, including oral steroids, continuous use of topical steroid creams or ointments, or any inhaled steroids
• No concurrent anticoagulants, except to keep an indwelling line patent
• No other concurrent anticancer therapy, including chemotherapy, immunotherapy, radiotherapy, experimental programs, and/or surgery