Prospective Randomized Study of Cell Transfer Therapy for Metastatic Melanoma Using Tumor Infiltrating Lymphocytes Plus IL-2 Following Non-Myeloablative Lymphocyte Depleting Chemo Regimen Alone or in Conjunction With 12Gy Total Body Irradiation (TBI...

Background: * Adoptive cell therapy (ACT) using autologous tumor infiltrating lymphocytes can mediate the regression of bulky metastatic melanoma when administered along with high-dose aldesleukin (IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen consisting of cyclophosphamide and fludarabine. * In a series of consecutive trials using this chemotherapy preparative regimen alone or with 2 Gray (Gy) or 12 Gy total body irradiation (TBI) objective response rates using Response Evaluation Criteria in Solid Tumors (RECIST) criteria were 49%, 52%, and 72%, respectively. Complete regression rates in these three consecutive trials were 12%, 20%, and 40%, respectively strongly suggesting that the addition of TBI could improve the complete regression rate. Of the 20 complete regressions seen in this trial, 19 are on-going at 37 to 82 months. * Because of the complexity of developing selected TIL for use in adoptive transfer, we have recently developed a simplified method for producing TIL that is more applicable to use in outside institutions. Utilizing young TIL cells (sometimes with cluster of differentiation 8 (CD8) purification) in 105 patients, the objective response rate was 34% with a 6.6 % incidence of complete regressions. All patients in this trial received the cyclophosphamide fludarabine regimen alone. * Because of the strong suggestion that the addition of TBI to the chemotherapy regimen could increase durable, complete regression rates in patients with metastatic melanoma, we are now attempting to definitively determine whether the addition of TBI to the chemotherapy preparative regimen can improve complete response rates, and overall survival in patients receiving young TIL. Objectives: -To determine, in a prospective randomized trial, the complete response rate and survival of patients with metastatic melanoma receiving adoptive cell transfer (ACT) using young TIL plus aldesleukin treatment following either a chemotherapy preparative regimen alone, or the same chemotherapy preparative regimen plus TBI. Eligibility: -Patients who are 18 years or older must have: * Evaluable metastatic melanoma; * Metastatic melanoma lesion suitable for surgical resection for the preparation of TIL; * No contraindications to high dose aldesleukin administration or total body irradiation; * No concurrent major medical illnesses or any form of immunodeficiency Design: -Patients with metastatic melanoma will have lesions resected and after TIL growth is established patients with will be prospectively randomized to receive ACT with young TIL plus aldesleukin following either a non-myeloablative chemotherapy preparative regimen or this same regimen plus TBI.