RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Biological therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop tumor cells from growing. Aldesleukin may stimulate white blood cells to kill tumor cells. Giving cyclophosphamide together with cellular adoptive immunotherapy and aldesleukin may be an effective treatment for metastatic melanoma.

PURPOSE: This phase I trial is studying the side effects of cyclophosphamide, cellular adoptive immunotherapy, and aldesleukin in treating patients with metastatic melanoma.

OBJECTIVES:

Primary

• Assess the safety and toxicity of cyclophosphamide, adoptive immunotherapy comprising autologous CD8+ antigen-specific cytotoxic T-lymphocyte (CTL) clones, and aldesleukin in patients with metastatic melanoma.
• Assess the duration of in vivo persistence of adoptively transferred CD8+ CTL clones.

Secondary

• Evaluate the antitumor effect of this regimen in these patients.

OUTLINE: This is a nonrandomized study. Patients undergo leukapheresis or blood draws for collection of peripheral blood mononuclear cells for the generation of antigen-specific cytotoxic T-lymphocyte (CTL) clones. Patients are assigned to 1 of 2 treatment cohorts.

• Cohort I: Patients receive cyclophosphamide IV on days -3 and -2 and autologous CD8+ CTL clones IV over 30-60 minutes on day 0. Patients also receive high-dose aldesleukin subcutaneously (SC) 3 times a day on days 0-5 in the absence of disease progression or unacceptable toxicity.
• Cohort II: Patients receive cyclophosphamide and autologous CD8+ CTL clones as in cohort I. Patients receive low-dose aldesleukin SC twice daily on days 0-14 in the absence of disease progression or unacceptable toxicity.

After the completion of study treatment, patients are followed periodically for at least 1 year.

PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic melanoma

  • Progressive disease after conventional therapy
• HLA-A2, B44, or A24 positive disease
• Bidimensionally measurable disease

• No current CNS metastases

  • Previously treated CNS metastases may be allowed provided there is no recurrence within the past 2 months

PATIENT CHARACTERISTICS:

• Zubrod performance status 0
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Creatinine ≤ 1.6 mg/dL OR creatinine clearance ≥ 75 mL/min
• AST ≤ 3 times upper limit of normal
• Bilirubin ≤ 1.6 mg/dL
• PTT ≤ 1.5 times control
• Able to tolerate high-dose cyclophoshamide (cohorts I and II) and high-dose aldesleukin (cohort I)

• Must meet the following criteria to undergo leukapheresis:

  • Pulse > 40 or < 120
  • Weight ≥ 45 kg
  • Temperature ≤ 100.4 F°
  • WBC ≥ 3,000/mm³
  • Hematocrit ≥ 30%
  • Platelet count ≥ 100,000/mm³

• No clinically significant pulmonary dysfunction, including any of the following:

  • FEV_1 < 2.0 L
  • DLCO < 75%

• No significant cardiovascular abnormalities, including any of the following:

  • Congestive heart failure
  • Clinically significant hypotension
  • Symptoms of coronary artery disease
  • Presence of cardiac arrhythmias on EKG requiring drug therapy
  • Ejection fraction < 50% by echocardiogram or MUGA
• No active infections or oral temperature > 38.2°C within the past 72 hours
• No systemic infection requiring chronic maintenance or suppressive therapy
• No clinically significant autoimmune disorders or conditions of immunosuppression
• No AIDS, HIV-1-associated complex, or known HIV antibody seropositivity
• No recent hepatitis positivity by polymerase chain reaction

• Normal cardiac stress within the past 182 days required for patients with any of the following:

  • Over 50 years old
  • Abnormal EKG
  • Personal or family history of cardiac disease
  • Hypercholesterolemia
  • Hypertension

PRIOR CONCURRENT THERAPY:

• At least 24 hours since prior and no concurrent antihypertensive medications during aldesleukin therapy
• At least 3 weeks since prior chemotherapy, radiotherapy, or immunosuppressive therapy
• At least 3 weeks since prior experimental drugs and recovered
• No concurrent systemic steroids

• No other concurrent immunotherapy, including any of the following:

  • Interleukin
  • Interferon
  • Melanoma vaccines
  • Intravenous immunoglobulin
  • Expanded polyclonal tumor-infiltrating lymphocytes or lymphokine-activated killer cell therapy
• No concurrent pentoxifylline
• No other concurrent investigational agents