Open Study of Phase I / II Evaluating Tolerance and Efficacy of Mobilization and Collection of Peripheral Hematopoietic Stem Cells Device After a Single Injection of 0.24mg/kg of Plerixafor in Sickle Cell Patients

Sickle cell disease is a genetic disorder caused by a point mutation in the coding region of the gene of beta-globin with the consequence the production of an abnormal (betas-globin). This mutation is responsible for the polymerization of deoxygenated HbS chains. Polymers make red blood cells (RBC) rigid, and change their shapes and are responsible of structural lesions of the membrane, altering the rheological properties of the RBC and altering blood flow of microcirculation. The two ultimate consequences of all these changes are intravascular haemolysis and the occurrence of vaso-occlusive episodes. Allogeneic hematopoietic stem cells (HSC) transplantation is the only curative treatment for these patients, but only 25% of them have a HLA-genoidentical family donor. In the absence of a compatible donor, gene therapy with model autograft could be a valid alternative. However, gene therapy for the curative treatment of sickle cell disease requires an optimal number of genetically modified HSC to reinject the patient. In contrast to beta-thalassemia patients, the mobilization of HSC in peripheral blood by growth factors such as G-CSF in patients with sickle cell can trigger a vaso-occlusive crisis.

The onset of action of plerixafor is very fast. In pharmacodynamic studies in healthy volunteers, mobilization peak of CD34 + cells was observed between 6 and 9 hours after administration of plerixafor. One injection per day for 1 to 2 days should be sufficient to achieve an optimal collection (unlike the 5-6 days required for mobilization of HSC in G-CSF used as the only growth factor). The duration of exposure to risk is thereby theoretically reduced.

We propose an drug test - Phase I/II trial - monocenter- non-comparative - not randomized - uncontrolled - Open.

In this protocol, we propose to assess the safety and efficacy of peripheral HSC mobilization in three major sickle cell patients (SS or Sbeta thalassemia) (or five, if results of the first 3 patients are not reproducible) by a single injection of plerixafor after significant decrease of HbS rate. Adequate number of CD34 + cells collected will be a key point in the success of possible and subsequent autologous graft of genetically modified HSC; a dose> 3.106 cells / kg CD34 + is necessary. Mobilized and collected cells will be stored for a possible future gene therapy or as not handled backup graft.

These three patients will be included sequentially; new inclusion will take place only if no serious adverse events have occurred in patients being participated in the trial. Recruitment will take place during the consultation in Apheresis Therapeutic Unit / Department of Biotherapy at the Necker-Enfants Malades Hospital. Patients being recruited from the cohort of adults with sickle cell disease at the Hospital Necker-Enfants Malades, the principal investigator will have seen the patient in consultation in the weeks preceding the decision to propose him to take part in research. This consultation will constitute within the framework of this protocol, prior medical examination.