Vaccine Therapy in Treating Patients With Refractory Metastatic Melanoma

Immunization Of HLA-A*0201 or HLA-DPB1*04 Patients With Metastatic Melanoma Using Epitopes From The ESO-1 Antigen

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. PURPOSE: Randomized phase II trial to study the effectiveness of vaccine therapy in treating patients who have refractory metastatic melanoma.

OBJECTIVES: Determine whether an immunologic response can be obtained after administration of ESO-1 peptide vaccine comprising class I , II, or both peptides in HLA-A*201 or HLA-DPB1*04 positive patients with refractory metastatic melanoma expressing ESO-1. Determine the toxicity of this vaccine in these patients. Determine whether prior immunization with this vaccine results in increased clinical responsiveness in patients treated with interleukin-2. OUTLINE: Patients are assigned to 1 of 3 groups according to HLA type. Group 1 (HLA-A*201 and HLA-DPB1*04 positive): Patients receive ESO-1 peptide vaccine comprising class I (ESO-1:157-165 [165V]) and class II (ESO-1:161-180) peptides subcutaneously once every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Group 2 (HLA-A*201 positive and HLA-DPB1*04 negative):Patients receive ESO-1 peptide vaccine as in group I comprising class I peptide only. Group 3 (HLA-A*201 negative and HLA-DPB1*04 positive):Patients receive ESO-1 peptide vaccine as in group I comprising class II peptide only. Patients who develop disease progression discontinue vaccinations and receive high-dose interleukin (IL-2) IV over 15 minutes every 8 hours for up to 4 days (maximum of 12 doses). Treatment with IL-2 repeats every 10-14 days for 4 courses in the absence of disease progression (after at least 2 courses) or unacceptable toxicity. Patients who have stable disease or a mixed or partial response to vaccination or IL-2 therapy may be eligible for additional vaccine therapy. Patients who have a complete response to vaccine therapy are eligible for 1 additional treatment. Patients are followed at 3 weeks. PROJECTED ACCRUAL: A total of 45-90 patients (15-30 per treatment group) will be accrued for this study within 1 year.

DISEASE CHARACTERISTICS: Diagnosis of metastatic melanoma that expresses ESO-1 antigen Must have progressed during prior standard treatment Measurable or evaluable disease HLA-A*201 or HLA-DPB1*04 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: SGOT and SGPT less than 3 times normal Bilirubin no greater than 1.6 mg/dL (3.0 mg/dL for patients with Gilbert's syndrome) Hepatitis B surface antigen negative Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: No cardiac ischemia* No myocardial infarction* No cardiac arrhythmias* NOTE: *For interleukin-2 (IL-2) administration Pulmonary: No obstructive or restrictive pulmonary disease (for IL-2 administration) Immunologic: No autoimmune disease No active primary or secondary immunodeficiency HIV negative No active systemic infections Other: Not pregnant Negative pregnancy test Fertile patients must use effective contraception No other active major medical illness (for IL-2 administration) PRIOR CONCURRENT THERAPY: Biologic therapy: No prior ESO-1 immunization Chemotherapy: Recovered from any prior chemotherapy Endocrine therapy: No concurrent systemic steroid therapy Radiotherapy: Recovered from any prior radiotherapy Surgery: Not specified Other: At least 3 weeks since any prior systemic therapy for cancer No other concurrent systemic therapy for cancer

Khong HT, Yang JC, Topalian SL, Sherry RM, Mavroukakis SA, White DE, Rosenberg SA. Immunization of HLA-A*0201 and/or HLA-DPbeta1*04 patients with metastatic melanoma using epitopes from the NY-ESO-1 antigen. J Immunother. 2004 Nov-Dec;27(6):472-7. doi: 10.1097/00002371-200411000-00007.