Melanoma (Skin)
Conditions
Keywords
stage IV melanoma, recurrent melanoma
Brief summary
RATIONALE: Biological therapies such as cellular adoptive immunotherapy use different ways to stimulate the immune system and stop cancer cells from growing. Fludarabine may help the immune system kill more cancer cells. PURPOSE: Phase I trial to study the effectiveness of fludarabine followed by cellular adoptive immunotherapy in treating patients who have metastatic melanoma.
Detailed description
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.
Interventions
BIOLOGICALtherapeutic autologous lymphocytes
DRUGfludarabine phosphate
Sponsors
National Cancer Institute (NCI)
Fred Hutchinson Cancer Center
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
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
Countries
United States
Outcome results
None listed