Cyclophosphamide and Fludarabine Followed By an Autologous Lymphocyte Infusion and Interleukin-2 in Treating Patients With Refractory or Recurrent Metastatic Melanoma

DISEASE CHARACTERISTICS:

• Diagnosis of melanoma

  • Metastatic disease
• Measurable disease
• HLA-A2 negative disease
• Disease did not respond to OR recurred after completion of prior high-dose interleukin-2 (IL-2)
• Eligible to receive high-dose IL-2
• No tumor reactive cells available for cell transfer therapy

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count > 1,000/mm^3
• Platelet count > 100,000/mm^3
• Hemoglobin > 8.0 g/dL
• No coagulation disorders

Hepatic

• ALT and AST < 3 times upper limit of normal
• Bilirubin ≤ 2.0 mg/dL (< 3.0 mg/dL if due to Gilbert's syndrome)
• Hepatitis B surface antigen negative
• Hepatitis C antigen negative

Renal

• Creatinine ≤ 2.0 mg/dL
• No renal failure requiring dialysis due to toxic effects of prior IL-2 administration

Cardiovascular

• No myocardial infarction
• No cardiac arrhythmias
• No other major cardiovascular illness as evidenced by a positive stress thallium or comparable test
• Normal cardiac stress test (e.g., stress thallium, stress MUGA, dobutamine echocardiogram) AND LVEF ≥ 45% (for patients ≥ 50 years of age or who have a history of EKG abnormalities, symptoms of cardiac ischemia, or arrhythmias)

Pulmonary

• No obstructive or restrictive pulmonary disease
• No other major respiratory illness
• FEV_1 ≥ 60% of predicted (for patients with a prolonged history of cigarette smoking or symptoms of respiratory dysfunction)

Immunologic

• HIV negative
• Epstein-Barr virus positive
• No active systemic infection
• No autoimmune disease (e.g., autoimmune colitis or Crohn's disease)

• No immunodeficiency due to prior chemotherapy or radiotherapy

  • Recovered immune competence after prior chemotherapy or radiotherapy as evidenced by normal lymphocyte count and WBC and an absence of opportunistic infection
• No other major immune system disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 months after completion of study treatment

• No other toxic effects during prior IL-2 administration that would preclude redosing with IL-2, including the following:

  • Mental status changes that would require intubation
  • Bowel perforation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• At least 4 weeks since prior systemic therapy

Chemotherapy

• At least 6 weeks since prior nitrosoureas
• At least 4 weeks since prior systemic therapy

Endocrine therapy

• No concurrent systemic steroid therapy

Radiotherapy

• Not specified

Surgery

• Not specified