• Complete tumor regression [ Designated as safety issue: No ]
  
• Safety [ Designated as safety issue: Yes ]
  
• Cell survival [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine whether treatment with a myeloablative lymphocyte-depleting preparative regimen comprising chemotherapy and total-body irradiation followed by autologous tumor-reactive tumor-infiltrating lymphocytes, high-dose aldesleukin, and autologous stem cell transplantation results in complete clinical tumor regression in patients with metastatic melanoma.
• Evaluate the safety of this regimen in these patients.

Secondary

• Determine the survival in patients of infused cells following the administration of a myeloablative regimen, using analysis of the sequence of the variable region of the T-cell receptor or flow cytometry.

OUTLINE: Patients are stratified according to prior therapy with aldesleukin (yes vs no).

• Autologous stem cell collection: Patients receive filgrastim (G-CSF) subcutaneously (SC) twice daily for 7 days. Beginning on day 5 of G-CSF, patients undergo apheresis daily for up to 3 days. If an adequate number of stem cells are not collected, patients may receive 1 additional course of G-CSF mobilization and apheresis or undergo bone marrow harvest.
• Lymphocyte-depleting myeloablative preparative regimen: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 15-30 minutes on days -7 to -3. Patients also undergo total-body irradiation twice daily on days -3 to -1.
• Autologous lymphocyte infusion: Patients receive autologous tumor-reactive tumor-infiltrating lymphocytes IV over 20-30 minutes on day 0.
• Aldesleukin therapy: Patients receive high-dose aldesleukin IV over 15 minutes 3 times daily on days 0-4 (maximum of 15 doses).
• Autologous stem cell transplantation: Patients undergo autologous CD34+ stem cell or bone marrow transplantation on day 1 followed by G-CSF SC once daily until blood counts recover.

After completion of study therapy, patients are followed periodically.

PROJECTED ACCRUAL: A total of 108 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of metastatic melanoma
• Measurable disease
• Patients must have tumor-reactive cells obtained and evaluated while participating in a NCI Surgery Branch cellular adoptive therapy clinical trial (e.g., NCI-99-C-0158 or NCI-03-C-0162)
• Previously received aldesleukin AND has progressive or recurrent disease (required for the first 10 patients enrolled in the study)
• No symptomatic CNS lesions with a requirement for immediate treatment

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Life expectancy ≥ 3 months
• Absolute neutrophil count > 1,000/mm³ (without filgrastim [G-CSF] support)
• Platelet count > 100,000/mm³
• Hemoglobin ≥ 8 g/dL
• ALT and AST < 3 times upper limit of normal
• Creatinine ≤ 1.6 mg/dL
• Bilirubin ≤ 2 mg/dL (< 3 mg/dL for Gilbert's syndrome)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 4 months after completion of study treatment
• LVEF ≥ 45%
• DLCO ≥ 60% of predicted
• No coagulation disorders
• No active systemic infections

• No active major medical illnesses of the cardiovascular or respiratory system, as evidenced by any of the following:

  • Cardiac arrhythmias
  • Positive stress thallium or comparable test
  • Symptoms of cardiac ischemia
  • Myocardial infarction
  • Obstructive or restrictive pulmonary disease
• No history of EKG abnormalities

• No form of primary or secondary immunodeficiency

  • Recovered immune competence after chemotherapy or radiotherapy
• No other active major medical illness of the immune system
• No HIV positivity
• No hepatitis B or C
• Able to receive high-dose aldesleukin
• FEV_1 ≥ 60% of predicted for patients with prolonged history of cigarette smoking or symptoms of respiratory dysfunction

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 30 days since prior systemic therapy (6 weeks for nitrosoureas) and recovered
• Minor surgery within the past 3 weeks allowed if recovered
• No prior preparative regimens with cyclophosphamide and fludarabine while enrolled on prior NCI Surgery Branch cellular adoptive therapy clinical trials
• No prior anti-cytotoxic T lymphocyte antigen-4 (anti-CTLA-4) antibody unless a post anti-CTLA-4 antibody treatment colonoscopy was normal with a normal colonic biopsy
• No concurrent systemic steroid therapy
• No other concurrent investigational agents