Vaccine Treatment in Combination With IL-2 and Treated Lymphocytes for Advanced Melanoma

Background: Recent clinical studies in the Surgery Branch have demonstrated clinical responses in patients undergoing adoptive transfer of autologous tumor reactive lymphocytes following a non-myeloablative immunosuppressive chemotherapy regimen. Additional studies in the Surgery Branch using immunization with recombinant fowlpox virus after cell transfer in the immunosuppressed host have provided strong evidence to suggest that the adoptive transfer of lymphocytes in our clinical protocols in patients with melanoma will be substantially improved by the simultaneous administration of recombinant fowlpox virus. Objectives: The primary objective will be to determine whether gp100 reactive lymphocytes infused in conjunction with immunization with rf-gp100P209 and administration of high dose or low dose IL-2 may result in complete clinical tumor regression in patients with metastatic melanoma receiving a nonmyeloablative but lymphoid depleting preparative regimen. Secondary objectives will be to determine the survival in patients, of infused cells following this regimen, and to determine the safety of this regimen. Eligibility: Patients who are HLA-A201+ must be greater than or equal to 16 years of age and have measurable metastatic melanoma that is refractory to standard therapy. Safety laboratory values must be within defined parameters. More than four weeks must have elapsed since any prior systemic therapy. Patients must be eligible to receive IL-2 and may not have cardiac, pulmonary or other major medical illnesses. Patients may not be allergic to eggs or hypersensitivity to any agents used in this trial, must not require concomitant therapy with steroids. Design: Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine and then will be treated by the adoptive transfer of lymphocytes reactive with the gp100:209-217 melanoma antigen, immunization with intravenous fowlpox virus rF-gp100P209, and the administration of high dose or low dose IL-2. Approximately 28 days after the cell infusion, patients receiving high dose IL-2 will receive a second intravenous fowlpox virus rf-gp100P209 followed by administration of high dose IL-2. A complete evaluation of evaluable lesions will be conducted 6-8 weeks after cell infusion. Patients receiving low dose IL-2 will receive a second intravenous fowlpox virus rf-gp100P209 after the 6 weeks of injections and one week of rest followed by repeat administration of the six week cycle of low dose IL-2. A complete evaluation of evaluable lesions will be conducted 3 weeks after the last dose of low dose IL-2. For each of the two cohorts, a small optimal Phase II design will be used and will target 15% (p1=0.15) as a goal for complete response as opposed essentially zero probability normally associated with patients who relapse after high dose IL-2 alone (p0=0.02 will be used). Initially, 16 patients will be enrolled and evaluated in each cohort; if at least 1 of the first 16 patients has a complete response, then accrual to 29 patients will take place. It is expected that it will require 2-3 years to accrue all 58 patients to this study.