Prospective Randomized Comparative Study of Cell Transfer Therapy Using CD8+-Enriched Short-Term Cultured Anti-Tumor Autologous Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen Compared to High-Dose Aldesleukin in M...

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. * Although this adoptive cell therapy (ACT) has been shown capable of mediating objective clinical responses in patients with metastatic melanoma, including patients who have previously been treated with aldesleukin or chemotherapy, the treatment is only available in the Surgery Branch, National Cancer Institute (NCI) and in just one or two other institutions in the United States. * Despite our reports of the objective regressions in patients receiving adoptive cell therapy (ACT), doubts have been raised concerning the possible influence of patient selection bias that may have accounted for the increase in survival using ACT compared to historical controls. * ACT is a cumbersome and labor intensive procedure which has discouraged many from applying it. We have recently developed simplifications in the technique for generating TIL that are also capable of mediating objective responses. * To evaluate the efficacy of ACT we are now proposing a prospective randomized trial to compare this form of therapy with standard available treatment for patients with metastatic melanoma. Objectives: * To determine, in a prospective randomized trial, the response rate and progression free survival of patients with metastatic melanoma receiving either ACT or standard high-dose aldesleukin treatment. * Survival rate will be evaluated as a secondary endpoint. * To determine the toxicity of these two treatment regimens. Eligibility: Patients who are 18 years of age or older must have: * Evaluable metastatic melanoma; * No prior treatment with high-dose aldesleukin (greater than or equal to 600,000 IU IL-2 q8h or the equivalent) * No contraindications to high-dose aldesleukin administration; * No concurrent major medical illnesses or any form of immunodeficiency; * Lesions of at least 2cm in diameter that can be surgically removed with minimal morbidity. Design: * Prior to amendment D, patients with metastatic melanoma lesions that can be resected with minimal morbidity will be prospectively randomized to receive either ACT using CD8+ young TIL (arm 2) and aldesleukin (arm 1) following a non-myeloablative chemotherapy preparative regimen, or will receive standard high-dose aldesleukin therapy. * With the approval of amendment D, arm 1 and 2 will be closed, and two new arms will be opened. Patients with metastatic melanoma lesions that can be resected with minimal morbidity will be prospectively randomized to receive either ACT using young TIL (arm 4) and aldesleukin (arm 3) following a non-myeloablative chemotherapy preparative regimen, or will receive standard high-dose aldesleukin therapy. * Response rate and time to progression will be evaluated for all patients on an intent-to-treat basis. * Patients may crossover to the other treatment arm after progressive disease is documented by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, if still eligible.