Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Melanoma

BACKGROUND: \- Tumor Infiltrating Lymphocytes (TIL) can mediate the regression of bulky metastatic melanoma when administered to the autologous patient along with high-dose aldesleukin (IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen. * IL-2 administration has been shown to increase the number of T regulatory cells and in our trials we have found a direct relationship between the number of IL-2 doses and the reconstitution of patients at one week with cluster of differentiation 4 + forkhead box P3 (CD4+ Foxp3) + T regulatory cells. * In our analysis of factors that relate to the ability of this treatment to mediate objective responses, we have found a highly significant inverse correlation between reconstitution of CD4+ Foxp3+ T regulatory cells and the likelihood of achieving an objective response. * In our prior clinical trials of cell transfer using TIL after lymphodepletion with or without 2 (gray)Gy total body irradiation, patients who experienced an objective response received fewer doses of IL-2 compared to non-responders (p=0.007 and 0.03 respectively). * High levels of the homeostatic T cell growth factor, IL-15, are present in patient serum after the lymphodepleting regimen at the time of cell transfer. * These factors raise the possibility that IL-2 administration is not required after cell transfer. OBJECTIVES: * The primary objective of this trial is to determine whether objective responses can be mediated in patients with metastatic melanoma who have received a lymphodepleting chemotherapy regimen and adoptive transfer of young tumor infiltrating lymphocytes and no IL-2 administration. * The secondary objective involves the determination of the level of transferred cells in the blood that persist at about 1 week and 1 month after transfer. ELIGIBILITY: * Patients greater than or equal to 18 years old with pathologically confirmed diagnosis of metastatic melanoma. * Patients with measurable disease, absolute neutrophil count greater than 1000/mm(3) and platelet count greater than 100,000/mm(3). * Patients not eligible to receive IL-2. DESIGN: * Patients with metastatic melanoma will undergo resection to obtain tumor for generation of autologous TIL cultures. * Patients will receive a non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by the administration of young autologous TIL. \- Patients will be evaluated for objective clinical response and for persistence of the transferred cells.