Chemotherapy Followed by gp100 Lymphocytes and Aldesleukin to Treat Melanoma

Background: * Tumor infiltrating lymphocytes (TIL) transfer studies in patients with metastatic melanoma following lymphodepletion have resulted in 50% objective response rates with a 10-15% rate of complete responses. * Pre-clinical and clinical studies of adoptive immunotherapy have suggested that effective lymphocytes for transfer have high avidity for the target antigen, undergo limited in vitro antigen and IL-2 stimulation, and have high expression of cluster of differentiation 27+ (CD27+). * We have developed a novel in vitro strategy using high throughput polymerase chain reaction (PCR) screening to rapidly isolate low frequency antigen specific cluster of differentiation 8+ (CD8+) T cells from the peripheral blood repertoire that have these characteristics, and that recognize the gp100:154-162 epitope, an abundantly expressed melanoma antigen, presented by human leukocyte antigens (HLAA2) on the tumor surface. * The current proposed transfer of gp100:154-162 reactive lymphocytes administered in conjunction with a lymphodepleting preparative regimen and aldesleukin would represent a significantly novel approach to adoptive immunotherapy. Objectives: * To determine whether gp100:154-162 reactive cluster of differentiation 4+ (CD4+) T cell depleted lymphocytes infused in conjunction with the administration of high-dose aldesleukin or low-dose aldesleukin may result in clinical tumor regression in patients with metastatic melanoma receiving a non-myeloablative lymphoid depleting preparative regimen. * To evaluate the safety of the treatment in patients receiving the non-myeloablative conditioning regimen, cell transfer, and high-dose or low-dose aldesleukin. * To determine the survival in patients, of infused cells following the administration of the non-myeloablative regimen, using analysis of the sequence of the variable region of the T cell receptor or flow cytometry (fluorescence activated cell sorting-FACS). Eligibility: -Patients with refractory metastatic melanoma who are greater than or equal to 18 years of age, are HLA-A2+, who have gp100:154-162 reactive peripheral blood lymphocytes available and are physically able to tolerate non-myeloablative chemotherapy. Patients must be refractory to prior high dose aldesleukin treatment if they are medically eligible to receive it. Patients who can tolerate high-dose aldesleukin will receive it with cell infusion; those who cannot tolerate high-dose will receive low-dose aldesleukin. Design: * Patients will receive a non-myeloablative lymphocyte depleting preparative regimen consisting of cyclophosphamide (60 mg/kg/day X 2 days intravenous (IV)), fludarabine (25 mg/m\^2/day IV X 5 days). * Patients will receive intravenous adoptive transfer of gp100:154-162 reactive peripheral blood lymphocytes (minimum 1 X 10\^9) and up to a maximum of 3 X 10\^11) lymphocytes) followed by high-dose intravenous (IV) aldesleukin (720,000 IU/kg/dose every 8 hours for up to 15 doses) or low-dose subcutaneous (SQ) aldesleukin (125,000 IU IL-2/kg/dose for 5 days for 6 weeks with 2 days rest per week). * A complete evaluation of evaluable lesions will be conducted 4-6 weeks after the last dose of aldesleukin in the high dose arm and 2-4 weeks after the last dose of aldesleukin in the low dose arm. Patients will be enrolled into two cohorts. The cohort receiving high dose aldesleukin will be conducted using a small optimal two-stage Phase II design, initially 21 patients will be enrolled, and if two or more of the first 21 patients has a clinical response (partial response (PR) or complete response (CR)), accrual will continue to 41 patients, targeting a 20% goal for objective response. For the cohort who will receive low dose aldesleukin, the study will be conducted as a Minimax two-stage phase II trial. Initially 12 evaluable patients will be enrolled to this cohort, and if 1 or more the first 12 have a response, then accrual would continue until a total of 21 patients, targeting a 20% goal for objective response.