Lentiviral-mediated Gene Therapy of Fanconi Anemia Patients Subtype A

Clinical Trial Phase I / II to Evaluate the Safety and Efficacy of the Infusion of Autologous CD34 + Cells Transduced With a Lentiviral Vector Carrying the Gene FANCA in Patients With FA Subtype A (FANCOLEN-1)

This is an open, Phase I / II clinical trial to evaluate the safety and efficacy of a hematopoietic gene therapy procedure with an orphan drug consisting of a lentiviral vector carrying the FANCA gene for patients with Fanconi Anemia of Subtype A .

CD34 + cells derived from bone marrow and / or mobilized peripheral blood (fresh and / or cryopreserved) from patients with Fanconi subtype A (FA-A), will be transduced ex vivo with a lentiviral vector carrying the gene FANCA (orphan drug) . After transduction the cells will be inoculated in patients in order to restore their hematopoiesis with genetically corrected stem cells.

The main objective of this open-label Phase I / II clinical trial is to evaluate the safety and therapeutic efficacy of a hematopoietic gene therapy procedure with an orphan drug consisting of a lentiviral vector carrying the FANCA gene for patients with Fanconi's Anemia Subtype A.

The drug to be administered to the patients consists of the cellular product resulting from the transduction of autologous CD34 + cells with the therapeutic lentiviral vector PGK-FANCA.Wpre *.

The dose of cells to infuse in the patients will be that obtained from the transduction process of between 3x10^5 and 4x10^6 CD34 + cells / kg of patient body weight.

The cells will be infused intravenously in a single dose, after complete the transduction process.

Follow-up period: 3 years after infusion of transduced cells. However, patients will be monitored outside the clinical trial over a 10-year period.

Follow-up of the grafted transduced cells will be performed on peripheral blood and bone marrow samples.

Inclusion Criteria:

• Patients diagnosed with Fanconi Anemia complementation group A (FA-A)
• Minimum age 1 year
• Maximum age 21 years
• Lansky Index> 60%.
• Informed consent in accordance with current legal regulations.
• Number of cells to be transduced: At least 3x10^5 purified CD34+ / kg body weight.
• Negative result in the urine pregnancy test at the baseline visit for women of childbearing age, who should be committed to using an effective contraceptive method during the period of study participation.

Exclusion Criteria:

• Patients with an human leukocyte antigen (HLA) identical family donor.
• Evidence of myelodysplastic syndrome or leukemia, or cytogenetic abnormalities predicting the same in bone marrow aspirates. In this case, the studies carried out two months in advance of the patient's entry into the clinical trial will be considered valid.
• Evidence that the patient to be infused has signs of somatic mosaicism, with hematologic improvement.
• Any illness or concomitant process that in the opinion of the investigator incapacitates the subject for their participation in the study.
• Pre-existing sensory or motor impairment> = grade 2 according to the National Cancer Institute (NCl) criteria.
• Pregnant or lactating women.