Fludarabine Followed By Adoptive Immunotherapy in Treating Patients With Stage IV 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. Fludarabine may help the immune system kill more cancer cells. PURPOSE: Phase I trial to study the effectiveness of fludarabine followed by cellular adoptive immunotherapy in treating patients who have metastatic melanoma.

Detailed Description
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OBJECTIVES: Primary Determine the safety and toxicity of adoptive immunotherapy comprising autologous CD8+ antigen-specific cytotoxic T-lymphocyte (CTL) clones after fludarabine in patients with stage IV melanoma. Determine the duration of in vivo persistence of these CTL clones in these patients. Secondary Determine the antitumor effect of this regimen in these patients. OUTLINE: This is an open-label, nonrandomized study. Patients undergo leukapheresis or weekly phlebotomy for the collection of peripheral blood mononuclear cells from which autologous antigen-specific CD8+ cytotoxic T-lymphocyte (CTL) clones are generated. Patients receive autologous antigen-specific CD8+ CTL clones IV over 30-60 minutes on days 0 and 21 in the absence of rapid disease progression or unacceptable toxicity. Patients also receive fludarabine IV once daily on days 14-18. Patients are followed for up to 1 year. PROJECTED ACCRUAL: A total of 12 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 Following Fludarabine Lymphodepletion for Patients With Metastatic Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: therapeutic autologous lymphocytes
* Drug: fludarabine phosphate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed metastatic melanoma Stage IV disease HLA-A2 or -A3-expressing disease Bidimensionally measurable residual disease by palpation or radiographic imaging (e.g., x-ray or CT scan) No CNS metastases Previously treated CNS involvement allowed provided there is no evidence of CNS disease at least 2 months after completion of therapy PATIENT CHARACTERISTICS: Age 18 to 75 Performance status Karnofsky 80-100% Life expectancy More than 6 months Hematopoietic Platelet count > 100,000/mm^3 Absolute neutrophil count > 2,000/mm^3 Hepatic SGOT no greater than 3 times upper limit of normal Bilirubin no greater than 1.6 mg/dL INR no greater than 1.5 times normal Renal Creatinine no greater than 2.0 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular No congestive heart failure No clinically significant hypotension No symptoms of coronary artery disease No cardiac arrhythmia by EKG requiring drug therapy Pulmonary No clinically significant pulmonary dysfunction FEV_1 at least 1.0 L* DLCO at least 45%* NOTE: *For patients with a history of pulmonary dysfunction Immunologic No active infection No oral temperature greater than 38.2°C within the past 48 hours No systemic infection requiring chronic maintenance or suppressive therapy Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent immunotherapy (e.g., interleukins, interferons, melanoma vaccines, IV immunoglobulins, expanded polyclonal tumor-infiltrating lymphocytes, or lymphokine-activated killer therapy) Chemotherapy At least 3 weeks since prior chemotherapy (standard or experimental) Endocrine therapy No concurrent steroids 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: therapeutic autologous lymphocytes|nan|
|Drug: fludarabine phosphate|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