Biological Therapy in Treating Patients With Metastatic Melanoma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase I Study to Evaluate the Safety of Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen Specific T Cell Clones Targeting Cancer Testis Antigens 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: 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

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
Masking: None (Open Label)


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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recurrent melanoma, stage IV melanoma