Chemotherapy, Irradiation, Cell Infusions, and Interleukin-2 to Treat Metastatic Melanoma

INCLUSION CRITERIA: Patients must have tumor 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 Institutional Review Board (IRB) approved Surgery Branch adoptive cell therapy study, i.e. 99-C-0158 or 03-C-0162. The first ten patients enrolled must have previously received interleukin-2 (IL-2) and have been either non-responders (progressive disease) or have recurred. Patients must be greater than or equal to 18 years of age and must have measurable metastatic melanoma. 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 Eastern Cooperative Oncology Group (ECOG) 0, 1. Absolute neutrophil count greater than 1000/mm^3 without support of filgrastim. Platelet count greater than 100,000/mm^3. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than three times the upper limit of normal. Serum creatinine less than or equal to 1.6 mg/dl. Total bilirubin less than or equal to 2 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 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 or stable brain metastases will be eligible. Left ventricular ejection fraction (LVEF) greater than or equal to 45%. Carbon monoxide diffusing capacity (DLCO) greater than or equal to 60% predicted. CELL INFUSION EXCLUSION CRITERIA: Less than 30 days 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 eligibility criteria. Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria. 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. Hemoglobin less than 8 g/dl unable to be corrected with transfusion. Any active systemic infections, coagulation disorders or other active 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 ANC greater than 1000/mm^3 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 human immunodeficiency virus (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). Patients who are not willing to complete a durable power of attorney (DPA) will be excluded. Patients who have received prior preparative regimens with cyclophosphamide and fludarabine on prior Surgery Branch adoptive cell therapies will be excluded. The following patients will be excluded because of inability to receive high dose IL-2: Patients will be excluded if they have a history of electrocardiogram (EKG) abnormalities, symptoms of cardiac ischemia or arrhythmias and have a LVEF less than 45% on a cardiac stress test (stress thallium, stress multi-gated acquisition scan (MUGA), dobutamine, echocardiogram or other stress test). Similarly, patients who are 50 years old or greater with an LVEF less than 45% will be excluded. Patients who have a prolonged history of cigarette smoking or symptoms of respiratory dysfunction will be excluded if they have an abnormal pulmonary function test as evidenced by a forced expiratory volume 1 (FEV1) less than 60% predicted.