Fludarabine Followed By Adoptive Immunotherapy in Treating Patients With Stage IV Melanoma

OBJECTIVES:

Primary

• Determine the safety and toxicity of adoptive immunotherapy comprising autologous CD8+ antigen-specific cytotoxic T-lymphocyte (CTL) clones after fludarabine in patients with stage IV melanoma.
• Determine the duration of in vivo persistence of these CTL clones in these patients.

Secondary

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

OUTLINE: This is an open-label, nonrandomized study.

Patients undergo leukapheresis or weekly phlebotomy for the collection of peripheral blood mononuclear cells from which autologous antigen-specific CD8+ cytotoxic T-lymphocyte (CTL) clones are generated. Patients receive autologous antigen-specific CD8+ CTL clones IV over 30-60 minutes on days 0 and 21 in the absence of rapid disease progression or unacceptable toxicity. Patients also receive fludarabine IV once daily on days 14-18.

Patients are followed for up to 1 year.

PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic melanoma

• Stage IV disease
• HLA-A2 or -A3-expressing disease
• Bidimensionally measurable residual disease by palpation or radiographic imaging (e.g., x-ray or CT scan)
• No CNS metastases

• Previously treated CNS involvement allowed provided there is no evidence of CNS disease at least 2 months after completion of therapy

PATIENT CHARACTERISTICS:

Age

• 18 to 75

Performance status

• Karnofsky 80-100%

Life expectancy

• More than 6 months

Hematopoietic

• Platelet count > 100,000/mm^3
• Absolute neutrophil count > 2,000/mm^3

Hepatic

• SGOT no greater than 3 times upper limit of normal
• Bilirubin no greater than 1.6 mg/dL
• INR no greater than 1.5 times normal

Renal

• Creatinine no greater than 2.0 mg/dL OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• No congestive heart failure
• No clinically significant hypotension
• No symptoms of coronary artery disease
• No cardiac arrhythmia by EKG requiring drug therapy

Pulmonary

• No clinically significant pulmonary dysfunction
• FEV_1 at least 1.0 L*
• DLCO at least 45%* NOTE: *For patients with a history of pulmonary dysfunction

Immunologic

• No active infection
• No oral temperature greater than 38.2°C within the past 48 hours
• No systemic infection requiring chronic maintenance or suppressive therapy

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunotherapy (e.g., interleukins, interferons, melanoma vaccines, IV immunoglobulins, expanded polyclonal tumor-infiltrating lymphocytes, or lymphokine-activated killer therapy)

Chemotherapy

• At least 3 weeks since prior chemotherapy (standard or experimental)

Endocrine therapy

• No concurrent steroids

Radiotherapy

• At least 3 weeks since prior radiotherapy

Surgery

• Not specified

Other

• At least 3 weeks since prior immunosuppressive therapy
• No concurrent pentoxifylline
• No other concurrent investigational agents