biological therapy in treating patients with metastatic melanoma

Conditions: Melanoma (Skin)

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.

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.

Eligibility 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

Keywords: recurrent melanoma stage iv melanoma