HLA Haploidentical Bone Marrow Transplant in Patients With Severe Sickle Cell Disease
- Conditions
- Sickle Cell Disease
- Interventions
- Biological: bone marrow transplant
- Registration Number
- NCT03240731
- Lead Sponsor
- Centre Hospitalier Intercommunal Creteil
- Brief Summary
multicentric interventional biomedical research phase II, prospective, non-randomized evaluating a haploidentical marrow transplants after reduced-intensity conditioning and prevention of GvHD based on cyclophosphamide administration post transplantation in patients with severe sickle cell disease.
- Detailed Description
Sickle cell disease is a severe disease with frequent occurrence of painful crises and progressive installation of a multi organ injuries. Despite the progress in its management, particularly since the introduction of hydroxycarbamide, the median age of death in sickle cell patients was about 40 years in a recent US study. Severe forms resistant to hydroxyurea or cerebral vasculopathy require transfusion programs throughout susceptible to risks of iron overload and alloimmunization. The bone marrow transplantation cures almost 95% of children and adolescents transplant from an HLA-identical siblings. In patients without HLA-identical donor, interesting results have been reported in haploidentical transplants marrow without ex vivo T cell depletion taken after non myeloablative conditioning regimen and GvHD prevention with cyclophosphamide high dose injection after bone marrow transplant . This approach performed in 14 patients was effective to cure 50% of the patients and 50% have rejected the transplant . No death or severe GvHD were related to the procedure.
DREPHAPLO protocol aims to evaluate that approach in a population of sickle cell patients with severe complications of the disease, bringing direct benefit to patients with a cure of the disease in at least half of them.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 18
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description bone marrow transplant bone marrow transplant All the included patient will receive an haploidentical bone marrow transplant with the following protocol concerning the conditioning and GvHD prevention Conditioning * THYMOGLOBULINE : 0.5mg/kg at D-9 and 2 mg/kg at D-8 and D-7 * THIOTEPA: 10mg/kg/j at D-7 * CYCLOPHOSPHAMIDE (Endoxan®):14.5mg/kg/j at D-6 and D-5 * FLUDARABINE (Fludara®): 30mg/m2 per Day from D-6 to D-2 * TBI : 2GY : D -1 Graft : Injection at D0 of G-CSF-stimulated bone marrow transplant. Prophylaxis of GvHD * CYCLOPHOSPHAMIDE (Endoxan®): 50mg/Kg per Day from D+3 to D+4 * Sirolimus and MycophénolateMofétil (MMP) from D+5. In the absence of acute GvHD (aGvHD), stop of MMP to D35 and pursuit of sirolimus 1 year after the graft.
- Primary Outcome Measures
Name Time Method Survival rate 2 years Survival without sickle cell survival rate (electrophoresis of hemoglobin similar to that from the donor, that is to say a percentage of HbS not exceeding 10% of that of distance donor transfusions and that of a stable manner and without GvHDc other than mild
- Secondary Outcome Measures
Name Time Method occurrence of infectious complications at month 24 hemoglobin electrophoresis at 24 months ferritin dosage at month 6 Evaluation of iron overload by ferritin
occurrence of secondary cancer at month 24 ECOG score value 2 years Index Trading ECOG complete physical examination with determination of weight
Survival rate 1 year Survival without sickle cell survival rate (electrophoresis of hemoglobin similar to that from the donor, that is to say a percentage of HbS not exceeding 10% of that of distance donor transfusions and that of a stable manner and without GvHDc other than mild
occurence of graft versus host disease at month 24 evaluated monthly from M1 to M6, and M9, M12, M24
Chimerism at month 24 Chimerism in the peripheral blood of the total population and the CD3 + population with the techniques usually employed by the centers
occurrence of toxic deaths at month 24 Lymphocyte immunophenotyping 2 years Lymphocyte immunophenotyping T, B and NK + The Extended Phenotype including activation markers, assessment of naive people and memories, T reg populations etc) and plasma protein electrophoresis: 1 month, 3 months, 6 months, 12 months and 24 months post-transplantation.
Assessment of sickle cell disease complications at 1 year Microalbuminuria, creatinuria; echocardiography for measurement of systolic ventricular ejection fraction (February), PAH research and measurement IT Vmax; respiratory function tests with measurement of DLCO; MRI brain with ARM and Cervical Pre-transplant anomalies; Radio of the pelvis
haematologic reconstitution 2 years defined as a neutrophil count\> 500 / mm3 and platelets\> 20000 / mm3, for three consecutive days.
grade of graft versus host disease at month 24 Incidence and grade of GvHD, toxic deaths and infectious complications and secondary cancer
MRI iron overload at 12 months hepatic and cardiac MRI to assess the iron overload
Trial Locations
- Locations (7)
Hospital Robert-Debré
🇫🇷Paris, France
Hospital Necker
🇫🇷Paris, France
CHU La Timone
🇫🇷Marseille, France
CHU Strasbourg
🇫🇷Strasbourg, France
Saint-Louis hospital
🇫🇷Paris, France
intercommunal hospital of Créteil
🇫🇷Créteil, France
CHU Henri-Mondor
🇫🇷Créteil, France