Melanoma (Skin)
Conditions
Keywords
recurrent melanoma, stage IV 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. Treating a person's white blood cells in the laboratory and then reinfusing them may cause a stronger immune response and kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of biological therapy in treating patients who have metastatic melanoma.
Detailed description
OBJECTIVES: Primary * Determine the safety and toxicity of cellular adoptive immunotherapy comprising autologous CD8+ cytotoxic T-lymphocyte clones targeting cancer-testis antigens in patients with metastatic melanoma. * Determine the duration of in vivo persistence of this therapy in these patients. Secondary * Evaluate the antitumor effects of this therapy in these patients. OUTLINE: Patients undergo leukapheresis to obtain peripheral blood mononuclear cells and then CD8+ cytotoxic T-lymphocyte (CTL) clones are generated ex vivo. Patients receive cellular adoptive immunotherapy comprising autologous CD8+ CTL clones targeting cancer testis antigens IV over 30 minutes on day 1. Patients also receive interleukin-2 subcutaneously every 12 hours on days 1-14 of courses 2-4. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients who demonstrate a clinical response after completion of the fourth course are eligible to receive additional T-cell infusions. Patients are followed for 9 months. PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study within 3 years.
Interventions
BIOLOGICALaldesleukin
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-A1, -A2, and -A3 positive * MAGE-1 or -3 positive by histology * Bidimensionally measurable disease by palpation on clinical examination, x-ray, or CT scan * No CNS metastases PATIENT CHARACTERISTICS: Age * 18 to 75 Performance status * Karnofsky 80-100% Life expectancy * More than 6 months Hematopoietic * Not specified Hepatic * Bilirubin ≤ 1.6 mg/dL * SGOT ≤ 3 times upper limit of normal * PT ≤ 1.5 times control Renal * Creatinine ≤ 2.0 mg/dL * Calcium ≤ 12 mg/dL Cardiovascular * No congestive heart failure * No clinically significant hypotension * No symptoms of coronary artery disease * No cardiac arrhythmias on electrocardiogram requiring drug therapy * Patients with prior cardiovascular disease or the presence of any of the above abnormalities undergo a cardiac evaluation, which may include a stress test and/or echocardiogram Pulmonary * No clinically significant pulmonary dysfunction by medical history or physical examination * FEV\_1 ≥ 60% of normal * DLCO ≥ 55% (corrected for hemoglobin) Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No retinitis or choroiditis * No active infections or oral temperature greater than 38.2 degrees Celsius within the past 72 hours * No systemic infection requiring chronic maintenance or suppressive therapy PRIOR CONCURRENT THERAPY: Biologic therapy * No other concurrent immunotherapy (e.g., other interleukins, interferons, melanoma vaccines, intravenous immunoglobulin, or expanded polyclonal tumor-infiltrating lymphocytes or lymphokine-activated killer cell therapy) Chemotherapy * At least 3 weeks since prior standard or experimental chemotherapy * 1-2 courses of prior cytoreductive chemotherapy for bulky disease allowed Endocrine therapy * No concurrent systemic steroids (except for toxicity management) 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