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 cancer cells from growing. PURPOSE: Phase I/II trial to study the effectiveness of biological therapy in treating patients who have metastatic melanoma.

Detailed Description
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OBJECTIVES: Assess the safety and toxicity of cellular adoptive immunotherapy using autologous CD8+ antigen-specific T-cell clones in patients with metastatic melanoma. Estimate the duration of in vivo persistence of adoptively transferred CD8+ antigen-specific cytotoxic T-cell clones in these patients. Evaluate the antitumor effects of CD8+ antigen-specific T-cell clones in these patients. OUTLINE: Autologous peripheral blood mononuclear cells are harvested and then CD8+ cytotoxic T-lymphocyte (CTL) clones targeting melanosomal antigens are generated ex vivo. Patients receive cellular adoptive immunotherapy comprising autologous CD8+ CTL clones over 30 minutes on day 1. Patients also receive interleukin-2 subcutaneously every 12 hours on days 1-14 of courses 2-3. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients are followed for approximately 1 year after the last infusion. PROJECTED ACCRUAL: Approximately 20 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 GENETICALLY MODIFIED AND UNMODIFIED AUTOLOGOUS CD8+ TYROSINASE-SPECIFIC T CELLS FOR PATIENTS WITH METASTATIC MELANOMA

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: aldesleukin
* Biological: therapeutic tumor infiltrating lymphocytes


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histopathologically proven metastatic melanoma No CNS metastases HLA-A2 positive Bidimensionally measurable disease by palpation on clinical exam or radiographic imaging (x-ray, CT scan, or MRI) Surgically accessible site for tumor cell procurement (skin, subcutaneous nodule, or superficial node) and patient clinically eligible for such surgery PATIENT CHARACTERISTICS: Age 18 to 75 Performance status Karnofsky 80-100% 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 Bilirubin no greater than 1.6 mg/dL SGOT no greater than 150 IU (or no greater than 3 times normal) Prothrombin time no greater than 1.5 times control Renal Creatinine no greater than 2.0 mg/dL Calcium no greater than 12 mg/dL Cardiovascular No congestive heart failure No clinically significant hypotension No symptoms of coronary artery disease No arrhythmia on EKG requiring drug therapy Pulmonary No severe chronic obstructive pulmonary disease FEV_1 at least 1.0 L DLCO at least 45% of predicted Other No active infection or oral temperature greater than 38.2 degrees C within 72 hours of study No systemic infection requiring chronic maintenance or suppressive therapy HIV negative No history of seizures No retinitis or choroiditis Not pregnant or nursing Negative pregnancy test Fertile patients must use adequate contraception Peripheral blood samples available weekly for 4 consecutive weeks PRIOR CONCURRENT THERAPY: Biologic therapy At least 4 weeks since other prior immunotherapy Chemotherapy 1 or 2 courses of cytoreductive chemotherapy allowed for bulky disease At least 4 weeks since prior standard or investigational chemotherapy Endocrine therapy At least 4 weeks since prior steroid therapy Radiotherapy At least 4 weeks since prior radiotherapy Surgery Not specified Other At least 4 weeks since other prior investigational drug therapy and recovered

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: aldesleukin|nan|
|Biological: therapeutic tumor infiltrating 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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stage IV melanoma, recurrent melanoma