Phase I Pilot Study of CD34 Enriched, Fanconi's Anemia Complementation Group C Gene Transduced Autologous Peripheral Blood Stem Cell Transplantation in Patients With Fanconi's Anemia

Study Overview
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Brief Summary
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OBJECTIVES: I. Determine the safety of transferring the Fanconi anemia complementation group C (FACC) gene to hematopoietic progenitors by retroviral mediated gene transfer in patients with Fanconi's anemia, complementation group C. II. Determine the extent of engraftment following this treatment regimen without prior ablation of recipient marrow in these patients. III. Determine the ability of this treatment regimen to correct the cell phenotype and improve hematopoietic function in these patients.

Detailed Description
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PROTOCOL OUTLINE: Patients receive filgrastim (G-CSF) subcutaneously daily on days 0-6 followed by apheresis to collect peripheral blood stem cells (PBSC) on days 5-7. PBSCs are processed in vitro for enrichment of CD34 cells and transduced with a Fanconi's anemia complementation C (FACC) retroviral vector on days 5-10. Patients receive transduced PBSCs IV over no more than 2 hours on days 8-10. PBSC infusions may be repeated no more than every 2 months for up to 4 courses total. Patients are followed monthly for 3 months, every 3 months for 9 months, every 6 months for the next year, and then yearly thereafter.

Conditions
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Fanconi's Anemia

Intervention / Treatment
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* Drug: filgrastim
* Genetic: Autologous stem cells transduced with FACC retroviral vector
* Procedure: Autologous Stem Cell Transplantation


Participation Criteria
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Eligibility Criteria
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PROTOCOL ENTRY CRITERIA: --Disease Characteristics-- Fanconi's anemia, complementation group C (FACC) Confirmed by diepoxybutane or mitomycin testing AND DNA analysis indicating FACC mutations Patients at least 25 kg weight No acute leukemia OR Bone marrow aspirate with greater than 10% blasts No patients who elect bone marrow transplantation --Prior/Concurrent Therapy-- At least 14 days since prior therapy for any acute viral, bacterial, or fungal infection --Patient Characteristics-- Performance status: Karnofsky 40-100% Hepatic: SGOT, SGPT, and alkaline phosphatase no greater than 5 times upper limit of normal (ULN) PT/PTT no greater than 1.5 times ULN Serum amylase no greater than 1.5 times ULN Bilirubin no greater than 2.5 mg/dL Triglyceride less than 400 mg/dL Renal: Creatinine clearance greater than 50 mL/min Cardiovascular: Normal cardiac function No ischemic heart disease that may be considered an anesthetic or operative risk Pulmonary: No lung disease that may be considered an anesthetic or operative risk Resting transcutaneous oxygen saturation greater than 90% on room air Other: HIV negative Hepatitis B surface antigen negative No underlying condition that may preclude study therapy (e.g., allergies to study reagents) No acute viral, bacterial, or fungal infection Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception

Ages Eligible for Study
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Minimum Age: 5 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 |
| --- |
|Drug: filgrastim|nan|
|Genetic: Autologous stem cells transduced with FACC retroviral vector|nan|
|Procedure: Autologous Stem Cell Transplantation|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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Fanconi's anemia, aplastic anemia, hematologic disorders, rare disease