• Safety [ Designated as safety issue: Yes ]
  
• Duration of in vivo persistence of adoptively transferred CD8+ cytotoxic T-lymphocyte clones [ Designated as safety issue: Yes ]
  

• Response [ Designated as safety issue: No ]
  

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 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

• 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