Background: Recent clinical studies in the Surgery Branch have demonstrated clinical responses in patients undergoing adoptive transfer of autologous tumor reactive lymphocytes following a non-myeloablative immunosuppressive chemotherapy regimen. Additional studies in the Surgery Branch using immunization with recombinant fowlpox virus after cell transfer in the immunosuppressed host have provided strong evidence to suggest that the adoptive transfer of lymphocytes in our clinical protocols in patients with melanoma will be substantially improved by the simultaneous administration of recombinant fowlpox virus. Objectives: The primary objective will be to determine whether gp100 reactive lymphocytes infused in conjunction with immunization with rf-gp100P209 and administration of high dose or low dose IL-2 may result in complete clinical tumor regression in patients with metastatic melanoma receiving a nonmyeloablative but lymphoid depleting preparative regimen. Secondary objectives will be to determine the survival in patients, of infused cells following this regimen, and to determine the safety of this regimen. Eligibility: Patients who are HLA-A201+ must be greater than or equal to 16 years of age and have measurable metastatic melanoma that is refractory to standard therapy. Safety laboratory values must be within defined parameters. More than four weeks must have elapsed since any prior systemic therapy. Patients must be eligible to receive IL-2 and may not have cardiac, pulmonary or other major medical illnesses. Patients may not be allergic to eggs or hypersensitivity to any agents used in this trial, must not require concomitant therapy with steroids. Design: Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine and then will be treated by the adoptive transfer of lymphocytes reactive with the gp100:209-217 melanoma antigen, immunization with intravenous fowlpox virus rF-gp100P209, and the administration of high dose or low dose IL-2. Approximately 28 days after the cell infusion, patients receiving high dose IL-2 will receive a second intravenous fowlpox virus rf-gp100P209 followed by administration of high dose IL-2. A complete evaluation of evaluable lesions will be conducted 6-8 weeks after cell infusion. Patients receiving low dose IL-2 will receive a second intravenous fowlpox virus rf-gp100P209 after the 6 weeks of injections and one week of rest followed by repeat administration of the six week cycle of low dose IL-2. A complete evaluation of evaluable lesions will be conducted 3 weeks after the last dose of low dose IL-2. For each of the two cohorts, a small optimal Phase II design will be used and will target 15% (p1=0.15) as a goal for complete response as opposed essentially zero probability normally associated with patients who relapse after high dose IL-2 alone (p0=0.02 will be used). Initially, 16 patients will be enrolled and evaluated in each cohort; if at least 1 of the first 16 patients has a complete response, then accrual to 29 patients will take place. It is expected that it will require 2-3 years to accrue all 58 patients to this study.
* INCLUSION CRITERIA: Patients must have gp100 reactive cells obtained and evaluated while participating in the Surgery Branch protocol, 'Cell Harvest and Preparation for Surgery Branch Adoptive Cell Therapy Protocols' or on another IRB approved Surgery Branch adoptive cell therapy study, i.e. 99-C-0158 or 03-C-0162. Patients must be greater than or equal to 16 years of age and must have measurable metastatic melanoma that is refractory to standard therapy, or has relapsed after standard therapy, including high dose IL-2 therapy. Patients must be HLA-A\*0201 positive. Patients of both genders must be willing to practice birth control during treatment and for four months after receiving the preparative regimen. Clinical performance status of ECOG 0, 1. Absolute neutrophil count greater than 1000/mm3 without support of filgrastim. Platelet count greater than 100,000/mm3. Hemoglobin greater than 8.0 g/dl (can be corrected with transfusion). Serum ALT/AST less than three times the upper limit of normal. Serum creatinine less than or equal to 2.0 mg/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. Must be willing to sign a durable power of attorney. Patients must be able to understand and sign the Informed Consent document. Patients with resected brain metastases will be eligible. Patients who are to receive high dose IL-2 and who are 50 years old or greater must have a normal stress cardiac test (stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test) with an LVEF greater than 45 percent. Patients who are to receive high dose IL-2 who have history of EKG abnormalities, symptoms of cardiac ischemia or arrythmias must have a normal stress cardiac test (stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test) with an LVEF greater than 45 percent. Patients who are to receive high dose IL-2 who have a prolonged history of cigarette smoking or symptoms of respiratory dysfunction must have a normal pulmonary function test as evidenced by a FEV(1) greater than 60 percent predicted. CELL INFUSION EXCLUSION CRITERIA: Less than four weeks has elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, or less than six weeks since prior nitrosurea therapy. All patients' toxicities must have recovered to a grade 1 or less or as specified in the above eligibility criteria. Patients may have undergone minor surgical procedures with the past 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria in section 2.1.1. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Life expectancy of less than three months. Systemic steroid therapy required. Any active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease. Any form of primary or secondary immunodeficiency. Must have recovered immune competence after chemotherapy or radiation therapy as evidenced by normal lymphocyte counts greater than 500 (grade 3 toxicity), normal ANC greater than 1000/mm3 and absence of opportunistic infections. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities.) Seropositive for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.) Patients with hepatitis B or hepatitis C will be excluded. Seronegative for Epstein-Barr virus (EBV). Allergy to eggs or any known hypersensitivity to any known agents on this trial. Patients who are not willing to complete a DPA will be excluded.