biological therapy in treating patients with metastatic melanoma

Conditions: Melanoma (Skin)

Summary: rationale: biological therapies use different ways to stimulate the immune system and stop tumor cells from growing. treating a person's white blood cells in the laboratory and 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 maximum tolerated dose of autologous cd4+ antigen-specific t-cells for cellular adoptive immunotherapy in patients with metastatic melanoma. * determine the safety and toxicity of this regimen in these patients. * determine the duration of in vivo persistence of adoptively transferred cd4+ antigen-specific t-cell clones in these patients. secondary * determine the antitumor effects of this regimen in these patients. outline: this is a dose-escalation study. patients undergo leukapheresis to collect peripheral blood mononuclear cells. cd4+ antigen-specific t-cell clones are generated over the next 2-3 months using immunogenic peptides mart1, tyrosinase, or gp100. patients receive autologous cd4+ antigen-specific t-cells iv over 30 minutes. cohorts of 3-6 patients receive escalating doses of autologous cd4+ antigen-specific t-cells until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. patients are followed on days 1 and 3 post t-cell infusion, and then once weekly for 12 weeks. projected accrual: a total of 3-18 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed metastatic melanoma * hla type expressing one of the following class ii alleles: * drb1\*0401 * drb1\*0404 * drb1\*1501 * dpb1\*0401 * dpb1\*0402 * tumor expresses tyrosinase * tumor expressing ny-eso-1 and are hla type dp4, dp2, or dr7 allowed * no cns metastases * prior cns involvement allowed provided there is no evidence of cns disease at least 2 months after treatment patient characteristics: age * 18 to 75 performance status * karnofsky 70-100% life expectancy * more than 16 weeks hematopoietic * wbc greater than 4,000/mm\^3 * absolute neutrophil count greater than 2,000/mm\^3 * platelet count greater than 100,000/mm\^3 * hematocrit greater than 30% hepatic * sgot no greater than 3 times upper limit of normal * inr no greater than 1.5 due to hepatic dysfunction * no significant hepatic dysfunction, defined as hepatic toxicity grade 2 or greater renal * creatinine no greater than 2.0 mg/dl or * creatinine clearance at least 60 ml/min * calcium no greater than 12 mg/dl cardiovascular * no significant cardiac abnormalities\*, defined by any 1 of the following: * congestive heart failure * clinically significant hypotension * symptoms of coronary artery disease * cardiac arrhythmias present on ekg requiring drug therapy note: \*patients with a history of cardiovascular disease or any of the above abnormalities undergo a cardiac evaluation, including a cardiac stress test and/or echocardiogram pulmonary * no clinically significant pulmonary dysfunction * fev1 at least 1.0 l or * fev1 at least 60% * dlco at least 55% (corrected for hemoglobin) immunologic * no acquired or hereditary immunodeficiency * no autoimmune disease * no active infection * no oral temperature greater than 38.2 degrees c within the past 72 hours * no systemic infection requiring chronic maintenance or suppressive therapy * hiv negative other * no retinitis or choroiditis * no history of seizures * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for 3 months after study prior concurrent therapy: biologic therapy * no other concurrent immunotherapy (e.g., interleukins, interferons, melanoma vaccines, iv immunoglobulin, or expanded polyclonal tumor-infiltrating lymphocytes or lymphokine-activated killer therapy) chemotherapy * at least 4 weeks since prior chemotherapy (standard or experimental) and recovered endocrine therapy * no concurrent systemic steroids except for toxicity management radiotherapy * at least 4 weeks since prior radiotherapy surgery * not specified other * at least 4 weeks since prior immunosuppressive therapy * more than 4 weeks since prior experimental drugs and recovered * no concurrent pentoxifylline * no other concurrent investigational agents

Keywords: recurrent melanoma stage iv melanoma