The purpose of this study is to compare the efficacy and safety of transplantation of gene modified autologous CD34+ cells in SCD patients within a therapeutic strategy that may include anti-inflammatory treatment as a pre-transplant treatment in case of severe inflammation detected at the inclusion analysis; the autologous CD34+ cell will be transduced by the bifunctional βAS3m/miR7m lentiviral vector expressing the therapeutical beta-globin, βAS3m, and the miRNA anti-HbS vs Standard Of Care (SOC).
Age 12 - 35 years
Diagnosis of HbSS by Hb electrophoresis and genetic analysis to analyse the alpha locus
Failed hydroxyurea (HU) therapy, were unable to tolerate HU therapy, OR inadequate clinical response to HU, defined as any one of the following outcomes, while on HU for at least 3 months: 2 or more acute sickle pain crisis requiring hospitalization, requirement of transfusion to maintain Hb >6.0g/dL, an episode of ACS despite adequate supportive care measures
Karnovsky/Lansky performance score ≥ 60%
Existence of a matched sibling donor
Based on myelogram, the presence of chromosomal (detected by karyotyping) or molecular abnormalities (detected by NGS) and retained dangerous by the Hemato-Oncology referent and validated during a specific multidisciplinary concerted meeting
Patients who have already been treated with gene therapy or BMT
Hematologic evaluation: Leukopenia (WBC <3,000/µL) or neutropenia (ANC <1,000/µL) or thrombocytopenia (platelet count <100,000/µL) within 90 days prior to mobilization or harvest (not due to an erytrapheresis procedure or possible acute viral infection)
Single group
standard of care
DrugSupportive management of VOC, long-term RBC transfusions, and foetal haemoglobin (HbF) induction with hydroxyurea (HU) Myocardic MRI (evaluation of function and fibrosis) + hematocrit measurement QoL questionnaires Imaging (brain MRI, transcranial and cervical ultrasound) Cardiac US, ECG Cardiac and Liver MRI (Fe assessment) Physical ability assessments Neuropsychological assessments Fertility
Disease-related mortality
All-cause mortality
Occurrence of vaso-occlusive events
Percentage of HbS
Measure of HbS
Percentage of HbF
Measure of HbF
Rate of Hemolysis
Biological parameters that reflect hemolysis : Total hemoglobin, Reticulocytes, lactate dehydrogenase LDH, circulating erythroblasts, haptoglobin, free plasmatic heme, no conjugated bilirubin, erythropoietin EPO
Rate of Anemia
Biological parameters that reflect anemia : Total hemoglobin, Reticulocytes, lactate dehydrogenase LDH, circulating erythroblasts, haptoglobin, free plasmatic heme, no conjugated bilirubin, erythropoietin EPO
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Assistance Publique - Hôpitaux de Paris
Lead sponsor
URC-CIC Paris Descartes Necker Cochin
Collaborator
Imagine Institute
Collaborator
Association Française contre les Myopathies (AFM), Paris
Collaborator
Marie Lannelongue Hospital
Collaborator
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