Melanoma Treatment With White Blood Cells That Destroy MART Expressing Tumor Cells

Background: * TIL transfer studies in patients with metastatic melanoma following lymphodepletion have resulted in 50 percent objective response rates with a 10-15 percent rate of complete responses. Despite these important clinical findings, adoptive cell transfer has not become widely available for patient treatment. Significant obstacles to this therapy are the need for invasive surgery and the inability of some patients to tolerate high dose aldesleukin. Further, the specific characteristics of the T cells that are responsible for the therapeutic effect of tumor infiltrating lymphocyte (TIL) are unknown, thus, resulting in significant treatment variability. * Pre-clinical and correlative clinical studies of adoptive immunotherapy have suggested putative favorable characteristics for transferred lymphocytes, such as, high avidity for the target antigen, limited in vitro stimulation, and high expression of CD27+. However, these characteristics have not been prospectively evaluated in human clinical trials. * We have developed a novel non invasive T cell isolation strategy using the heteroclitic MART-1:26-35(27L) peptide for in vitro sensitization of human PBL and high throughput quantitative polymerase chain reaction (qPCR) screening to rapidly isolate antigen specific cluster of differentiation 8 (CD8) + T cells from the cluster of differentiation 4 (CD4) + T cell depleted peripheral blood repertoire. These isolated T cells possess the above mentioned favorable characteristics and recognize the native MART-1:27-35 epitope, an abundantly expressed melanoma antigen presented by human leukocyte antigen serotype within HLA-A A serotype group (HLA-A2) on the tumor surface. * The current proposed transfer of these select MART-1:27-35 reactive lymphocytes in conjunction with a lymphodepleting preparative regimen with or without high dose aldesleukin would represent a novel therapeutic option for patients with advanced melanoma and provide a desperately needed option for patients who are not medically eligible for aldesleukin treatment. Objectives: * To determine whether MART-1:27-35 reactive lymphocytes infused with or without the administration of high-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 and cell transfer with or without the administration of high-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 MART-1:27-35 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 aldesleukin due to medical comorbidities or refuse high-dose aldesleukin will receive cell infusion without 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 MART-1:27-35 reactive peripheral blood lymphocytes (minimum 1 X 10\^8 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 no aldesleukin if they are not medically eligible to receive it. * A complete evaluation of evaluable lesions will be conducted 4-6 weeks after the last dose of aldesleukin in the aldesleukin arm and 4-6 weeks after the cell administration in the no aldesleukin 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 19 patients will be enrolled, and if 4 or more of the first 19 patients have a clinical response ((partial response ) PR or (complete response) CR), accrual will continue to 33 patients, targeting a 35 percent goal for objective response. For the cohort who will not receive 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 percent goal for objective response.