Use of IL-15 After Chemotherapy and Lymphocyte Transfer in 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. * 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 cluster of differentiation 4 (CD4)+ forkhead box P3 (Foxp3) + T regulatory cells and the likelihood of achieving an objective response. * Interleukin 2 (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 CD4+ Foxp3 + T regulatory cells. * Interleukin 15 (IL-15) is a strong T cell growth factor, but unlike IL-2, IL-15 is not involved in the generation and maintenance of CD4+ Foxp3 + T regulatory cells that can inhibit immune reactions. * In pre-clinical adoptive cell transfer studies utilizing a murine melanoma model, the administration of IL-15 following adoptive cell transfer improved anti-tumor effects. Objectives: * The primary objective of this trial is to determine the safety, toxicity, and maximum tolerated dose of intravenous recombinant IL-15 administered as a daily intravenous bolus for 10 consecutive days in patients with metastatic melanoma who have received a lymphodepleting chemotherapy regimen and adoptive transfer of tumor infiltrating lymphocytes. * An additional primary objective is to determine whether this combination is able to produce a modest number of clinical responses. * The secondary objective involves the determination of the level of reconstitution of T regulatory cells in patients who receive cell transfer followed by IL-15 and to determine the pharmacokinetics of IL-15 levels in the serum following intravenous administration. 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. * No serious comorbid conditions such as active systemic infections, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory or immune systems. 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 autologous Young TIL. In the phase 1 portion of this study, patients will receive recombinant human IL-15 at doses of 0.25, 0.5, 1 or 2 micrograms per kilogram give intravenously daily for 10 days starting on the day of cell transfer. One patient will be treated at the first dose level, if this patient experiences a dose limiting toxicity (DLT), additional patients will be treated at the dose to confirm that no greater than 1/6 patients have DLT prior to proceeding to the next higher level. If 2 DLTs are encountered in this cohort, the study will be terminated. In all other cohorts, groups of three to six patients will receive recombinant human IL-15. Should a single patient experience a dose limiting toxicity due to the cell transfer at a particular dose level, additional patients will be treated at the dose to confirm that no greater than 1/6 patients have a DLT prior to proceeding to the next higher level. If a level 2 or more DLTs in 3-6 patients has been identified, three additional patients will be accrued at the next-lowest dose, for a total of 6, in order to further characterize the safety of the maximum tolerated dose prior to starting the phase 2 portion. In the phase 2 portion of this study, patients will receive a non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by the administration of autologous Young TIL and IL-15 at the maximum tolerated dose (MTD) established in the phase 1 portion. * Studies will be performed to determine the reconstitution of patients with T regulatory cells and to determine the pharmacokinetics of IL-15 concentration in serum.