Mobilization and Collection of Peripheral Blood Stem Cells in Patients With Fanconi Anemia Using G-CSF and Plerixafor
Condition: Fanconi Anemia
MeSH terms: Fanconi Syndrome; Anemia; Fanconi Anemia
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to assess the feasibility of Plerixafor used in combination with
      G-CSF (Granulocyte Colony Stimulating Factor) in 5 Fanconi anemia patients to mobilize and
      collect a sufficient number of peripheral blood CD34+ cells for peripheral blood apheresis,
      for further gene therapy study.
    

Detailed description: 
      Fanconi anemia is an autosomal recessive disease with an average survival of around 24 years
      old. The number of cells producted by bone marrow decreases around 5-10 years old.
      Hematological symptoms occur around 7 years old. 80% of patients with Fanconi anemia have
      clinical signs of bone marrow failure in the first decade of life. Generally macrocytosis is
      the first noticeable sign. Then it leads to thrombocytopenia, anemia and pancytopenia.

      Epidemiologic studies show that nearly all of the patients will have medullar aplasia before
      40 years old, which is then the first cause of mortality.

      It must be emphasized that these complications may occur simultaneously for the same patient,
      so joint therapeutic intervention is needed.

      There is no basic treatment. Some currently used treatments cure cytopenias. These treatments
      involve blood transfusion, oral androgen, hematopoietic growth factor administration, such as
      Epo and G-CSF to treat anemia and neutropenia. These treatments are not curative.
      Hematopoietic stem cell transplantation is the only treatment able to restore permanently
      hematopoiesis. However, this treatment leads to a high level risk of developing solid tumors
      and other complications.

      All these data justify of developing a stem cells gene therapy treatment using a lentiviral
      vector expressing wild-type FANCA gene under CIBER promoter.

      Three studies have shown the potential number of cells to be mobilized in patients with
      Fanconi anemia.

      The aim is first, to show if administering G-CSF with plerixafor may lead to collect enough
      cells to potentially perform a gene therapy graft. Secondly the study will assess the
      tolerance, the stem cells' mobilization kinetic and collected cells' biological features.

      This study will be performed in Necker Children Hospital. 8 patients will be enrolled in
      order to reach 5 treated patients and to analyse how many injections and days are required to
      reach the cells' number goal.

      Sequential blood samples of patients will be drawn to monitor complete blood count (CBC),
      platelet, CD34+ cells rate and stem cells phenotype.

      The clinical and biological data will be anonymously entered in a electronic case report by
      the investigators up to the end of the study.
    

Intervention name(s): G-CSF; Plerixafor
Intervention type(s): Drug; Drug
Intervention description(s): D1 to D4 : Injection of 12 µg/kg of G-CSF twice a day . D5 : injection of 12 µg/kg of G-CSF (once/ twice a day according to cytapheresis's realization); D5 : injection of 24mg/kg of plerixafor once a day until cytapheresis has be done (maximum of 4 days)
Intervention MeSH terms: Plerixafor
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Fanconi Anemia; CD34+ cells mobilization; G-CSF; Plerixafor; gene therapy