Lymphodepletion Plus Adoptive Cell Transfer With High Dose IL-2 in Patients With Metastatic Melanoma

Inclusion Criteria: * Patients must have unresectable metastatic stage IV melanoma or stage III in-transit or regional nodal disease. * Residual measurable disease after resection of target lesion(s) for TIL growth * Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 -1. ECOG performance status of 0-1 will be inferred if the patient's level of energy is ≥ 50% of baseline. * Patients may be treatment-naïve or may have been previously treated for metastatic disease. * Patients with a negative pregnancy test (urine or serum) must be documented at screening for women of childbearing potential (WOCBP). * Adequate renal, hepatic and hematologic function, including creatinine of less than or equal to 1.7 gm/dL, total bilirubin less than or equal to 2.0 mg/dL, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dL, aspartic transaminase (AST) and alanine transaminase (ALT) of less than 3X institutional upper limit of normal (ULN), hemoglobin of 8 gm/dL or more, white blood count (WBC) of 3000 per mm³ and total granulocytes of 1000 per mm³ or more, and platelets of 100,000 per mm³ or more. * Patients must have a positive screening Epstein-Barr virus (EBV) antibody titre on screening test. * Patients with antibiotic allergies per se are not excluded; although the production of TIL for adoptive transfer includes antibiotics, extensive washing after harvest will minimize systemic exposure to antibiotics. * Patients that had previously grown sterile, validated TIL under Good Manufacturing Practices (GMP) conditions on Moffitt Clinical trial protocol 15375 (Use of Excess Melanoma Tumor Specimens Not Required for Diagnostic Purposes for Validation of Tumor Infiltrating Lymphocyte \[TIL\] Growth Procedures) meeting the above criteria may be consented and enrolled in the current trial using the previously established TIL stored in the Cell therapies Core facility for up to 2 years. * At screening, patients with ≤ 3 untreated central nervous system (CNS) metastases may be included provided none of the untreated lesions are \> 1 cm in greatest dimension, and there is no peri-tumoral edema present on brain imaging (magnetic resonance imaging \[MRI\] or computed tomography \[CT\] if MRI is contraindicated). * At screening, patients with CNS metastases treated with either surgical resection and/or radiation therapy may be included. Patients may be included if the largest lesion is ≤ 1 cm, and there is no evidence of progressive CNS disease on brain imaging at least 28 days after treatment. * At screening, patients may be included if the largest lesion is \> 1 cm or \> 3 in number, and there is no evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy. * All laboratory and imaging studies must be completed and satisfactory within 30 days of signing the consent document. Exclusion Criteria: * Patients with active systemic infections requiring intravenous antibiotics, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system are excluded. * Patients testing positive for human immunodeficiency virus (HIV) titre, Hepatitis B surface antigen, Hepatitis C antibody, Human T-lymphotropic virus (HTLV) I or II antibody, or both rapid plasma reagent (RPR) and fluorescein treponemal antibodies (FTA) positive are excluded. * Patients who are pregnant or nursing * Patients needing chronic, immunosuppressive systemic steroids * Patients with autoimmune diseases that require immunosuppressive medications * Presence of a significant psychiatric disease, which in the opinion of the principal investigator or his designee, would prevent adequate informed consent or render immunotherapy unsafe or contraindicated * Patients with \> 3 untreated CNS metastases or evidence of peri-tumoral edema will be excluded. * Patients with ≤ 3 untreated CNS metastases but with at least one lesion \>1 cm or peri-tumoral edema will be excluded. * Patients with treated CNS metastases \> 1 cm or \> 3 in number will be excluded if there is evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy. * Inability to comprehend and give informed consent