Clinical Phase II Trial to Evaluate CD34+ Cells Mobilization and Collection in Patients With Fanconi Anemia for Subsequent Transduction With a Lentiviral Vector Carring FANCA Gene. FANCOSTEM-1

Study Overview
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Brief Summary
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Fanconi anemia (FA) is a congenital disease characterized by bone marrow failure and increased incidence of malignant tumors. The Project pursue the optimization of the collection of hematopoietic progenitor cells for later use in another clinical trial entitled Clinical Trial Phase I/II to evaluate the safety and efficacy of the infusion of autologous CD34+ cells mobilized with mozobil and filgrastim, and transduced with a lentiviral vector carrying the FANCA gene (Orphan Drug) for patients with Fanconi Anemia Subtype A . The objectives of this study are, therefore, to assess the safety and efficacy of CD34+ cells mobilization with mozobil and filgrastim, which is postulated the most efficient for the collection of CD34+ cells from FA patients.

Official Title
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Clinical Phase II Trial to Evaluate Efficacy and Safety of CD34+ Cells Mobilization and Collection After Treatment With Plerixafor and Filgrastim in Patients With Fanconi Anemia for Subsequent Transduction With a Lentiviral Vector Carring FANCA Gene and Reinfusion in the Patient

Conditions
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Fanconi Anemia

Intervention / Treatment
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* Drug: filgrastim
* Drug: plerixafor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female > 1 year diagnosed of Fanconi's anemia confirmed by instability chromosomal test with diepoxy-butane or mitomycin C At least one of the following parameters must be higher than these values: Hemoglobin:8,0 g/dL; neutrophils: 750/mm3; platelets: 30.000/mm3 Lansky index> 60%. Left ventricular ejection fraction >50%. To grant informed consent in agreement with current law norms Women in childbearing age must obtain a negative result in the pregnancy test in serum or urine in the visit of selection and accept the use of suitable contraceptive methods since at least 14 days prior to the first dose of mobilizing treatment until the 14 days following the last Exclusion Criteria: Evidence of myelodysplastic syndromes or leukemia, or cytogenetic abnormalities predicted of these syndromes in bone marrow aspiration. Cytogenetic analyses performed 2 months before starting study are accepted Patients with active infection process or any other underlaying severe medical process Severe Functional alteration of organs (hepatic, renal, respiratory)(?3), according to National Cancer Institute (NCI CTCAE v3) criteria Haematopoietic transplant Any disease or concomitant process that is not compatible with the study as per investigator opinion Patients not elegible because of an psico-social evaluation Patients that received transfusional support during the last 3 months. Pregnant or breastfeeding women

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 64 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: plerixafor and filgrastim treatment<br>to assess the safety and efficacy of CD34+ cells mobilization with plerixafor and filgrastim | Drug: filgrastim<br>* G-CSF (12 μg/Kg/12 h) 8 days.<br>Drug: plerixafor<br>* Plerixafor 0,24 mg/kg/day after the fourth day of G-CSF, and until 5 cells CD34+/μL, max 4 doses of plerixafor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity of the mobilization procedure according to National Cancer Institute (CTC NCI, versión 3.0) | At a year (± 30 days) after the last apheresis, a complete physical examination, blood cell count, basic biochemistry and bone marrow aspirate will be done to the patient in order to control their general health status. | after 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients that reach >5 CD34+ cells/mcl after treatment with filgrastim and plerixafor | mobilization protocol will be determined by the percentage of patients who achieve peripheral blood counts exceeding 5 CD34+ cells /microliter | after 8 days | 
| Percentage of patients that reach a total CD34+ yield >4x10E6/kg, using the estimated weight of the patient in 5 years | the CD34+ cell collection protocol will be determined by the percentage of patients who reach at least one million CD34 + cells per kilogram of body weight projected to 5 years after the mobilization process | after 8 days | 
| Percentage of samples in which the recovery of CD34+ cells after the immunomagnetic selection procedure is >50% | the of CD34+ cell selection process will be determined by the proportion of immunoselected samples where the recovery of CD34 + cells is at least 50%, and where the final percentage of CD34+ cells is at least 50% | after 8 days | 
| Percentage of patients in which the CD34+ cells after the immunomagnetic selection is ³ 4x10E6/kg, using the projected weight at 5 years | will be determined by the percentage of patients who reach at least one million CD34 + cells per kilo of weight projected to 5 years after the immunomagnetic selection process of all the collected cells | after 8 days |