Biological Therapy in Treating Patients With Metastatic Melanoma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase I Study to Evaluate the Safety of Cellular Adoptive Immunotherapy Using Autologous CD4+ Antigen-Specific T Cell Clones for Patients With Metastatic Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: therapeutic autologous lymphocytes


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: therapeutic autologous lymphocytes|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent melanoma, stage IV melanoma