RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Biological therapies, such as cellular adoptive immunotherapy, work in different ways to stimulate the immune system and stop tumor cells from growing. Autologous stem cell transplant may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy. Interleukin-2 may stimulate a person's lymphocytes to kill tumor cells. Combining chemotherapy, radiation therapy, and biological therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cyclophosphamide and fludarabine together with radiation therapy followed by cellular adoptive immunotherapy, autologous stem cell transplant, and interleukin-2 works in treating patients with metastatic melanoma.

OBJECTIVES:

Primary

• Determine complete clinical tumor regression in patients with metastatic melanoma treated with a myeloablative lymphoid-depleting preparative regimen comprising cyclophosphamide, fludarabine, and total body irradiation followed by autologous tumor-reactive tumor-infiltrating lymphocyte infusion, autologous CD34+ stem cell transplantation, and low-dose or high-dose interleukin-2.
• Evaluate the safety of this regimen in these patients.

Secondary

• Determine the survival of the infused lymphocytes by analyzing the sequence of the variable region of the T-cell receptor or flow cytometry in patients treated with this regimen.

OUTLINE:

• Autologous stem cell collection: Patients receive filgrastim (G-CSF) subcutaneously (SC) twice daily for 8 days. Beginning on day 5 of G-CSF, patients undergo apheresis daily for up to 3 days. Patients may receive 1 additional course of G-CSF and apheresis or use stem cells stored from a prior stem cell harvest in order to obtain an adequate number of cells.

• Lymphocyte-depleting myeloablative preparative regimen: Patients receive cyclophosphamide intravenous (IV) over 1 hour on days -5 and -6 and fludarabine IV over 15-30 minutes on days -6 to -2. Patients also undergo total body irradiation on day -1.

• Autologous lymphocyte infusion: Patients receive autologous tumor-reactive tumor-infiltrating lymphocytes IV over 20-30 minutes on day 0* followed by G-CSF SC once daily until blood counts recover.

• Autologous stem cell transplantation: Patients receive autologous CD34+ stem cells IV on day 2.

• Interleukin therapy: Patients are assigned to 1 of 2 cohorts, depending on whether they have received prior high-dose interleukin-2 (IL-2).

  • Cohort 1 (patients who received prior high-dose IL-2): Beginning on day 0*, patients receive high-dose IL-2 IV over 15 minutes 3 times daily for up to 5 days (maximum of 15 doses).
  • Cohort 3 (patients who have not received prior high-dose IL-2): Patients receive treatment as in cohort 1.

NOTE: *Day 0 is 1-4 days after the last dose of fludarabine.

Patients are evaluated at 4-6 weeks.

PROJECTED ACCRUAL: A total of 116 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of metastatic melanoma
• Measurable disease
• Resected or stable brain metastases are allowed

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Eastern Cooperative Oncology Group (ECOG) 0-1

Life expectancy

• At least 3 months

Hematopoietic

• See Immunologic
• Absolute neutrophil count > 1,000/mm^3 (without support of filgrastim [G-CSF])
• Platelet count > 100,000/mm^3
• Hemoglobin ≥ 8 g/dL (transfusion allowed)
• No coagulation disorders

Hepatic

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 times upper limit of normal
• Bilirubin ≤ 2 mg/dL (< 3 mg/dL in patients with Gilbert's syndrome)
• No hepatitis B or C

Renal

• Creatinine ≤ 1.6 mg/dL

Cardiovascular

• Left ventricular ejection fraction (LVEF) ≥ 45% by cardiac stress test*
• No active major cardiovascular illness as evidenced by stress thallium or other comparable test
• No myocardial infarction
• No cardiac arrhythmias NOTE: *For patients ≥ 50 years of age receiving high-dose interleukin-2 (IL-2) OR patients with a history of electrocardiogram (EKG) abnormalities, symptoms of cardiac ischemia, or arrhythmias

Pulmonary

• Forced expiratory volume 1 (FEV_1) ≥ 60% of predicted by pulmonary function test in patients with prolonged history of cigarette smoking or symptoms of respiratory dysfunction*
• No active major respiratory illness
• No obstructive or restrictive pulmonary disease NOTE: *For patients receiving high-dose IL-2 only

Immunologic

• No active major immunologic illness

• No active systemic infections

• No primary or secondary immunodeficiency

  • Fully recovered immune competence after prior chemotherapy or radiotherapy as evidenced by both of the following:

    • Absolute neutrophil count > 1,000/mm^3
    • No opportunistic infections

• Human Immunodeficiency virus (HIV) negative

• Epstein-Barr virus positive

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 4 months after study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• At least 6 weeks since prior nitrosourea therapy
• No prior cyclophosphamide and fludarabine as part of a preparative regimen on National Cancer Institute (NCI) Surgery Branch adoptive cell therapy studies unless sufficient numbers of CD34+ stem cells (more than 2 x10^6/kg patient weight) have been obtained prior to the administration of chemotherapy

Endocrine therapy

• No concurrent systemic steroid therapy

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics
• Prior minor surgery within the past 3 weeks allowed if recovered

Other

• Recovered from all prior therapy
• At least 30 days since prior systemic therapy
• No other concurrent experimental agents