Biological Therapy in Treating Patients With Metastatic Melanoma

Fred Hutchinson Cancer Center18 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Purpose

TREATMENT

Enrollment

Conditions

Melanoma (Skin)

Interventions

therapeutic autologous lymphocytesBIOLOGICAL

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (1)

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Data from ClinicalTrials.gov

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