Comparison of Allogeneic Matched Related Haematopoietic Stem Cell Transplantation After a Reduced Intensity Conditioning Regimen With Standard of Care in Adolescents and Adults With Severe Sickle Cell Disease (DREPA-RIC)

A Prospective Multicenter Trial Comparing Allogeneic Matched Related Haematopoietic Stem Cell Transplantation After a Reduced Intensity Conditioning Regimen, With Standard of Care in Adolescents and Adults With Severe Sickle Cell Disease

Although the survival of children with sickle cell disease (SCD) has dramatically improved over the last decades in the US and Europe, mortality remains high in adults. Moreover, many children and most adults develop a chronic debilitating condition due to organ damage. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the unique curative approach; it allows the cure of more than 95% of children transplanted from a matched related donor (MRD) after a myeloablative conditioning regimen.To date, few studies have addressed the role of HSCT in SCD adults, due to the risk of graft versus host disease (GVHD) and to the toxicity expected in older patients with a higher risk of organ damage. The development of safe, non-myeloablative conditioning regimens that allow stable mixed chimerism and avoid GVHD appears as an attractive option for HSCT to cure adults with severe SCD. The investigators design a prospective multicenter trial targeting patients over 15 years with severe SCD, and compare non-myeloablative transplant (when a matched related donor (MRD) is identified) versus no HSCT (for patients lacking MRD). The main objective is to assess the benefit of HSCT on the 2-year event free survival compared to standard care. The primary endpoint is the 2-year event free survival.

Study Overview

• Status: Not yet recruiting
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Procedure: Allogeneic matched related haematopoietic stem cell transplantation; Other: Standard arm

• Study Type: Interventional
• Enrollment (Anticipated): 78
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Nathalie Dhedin; Phone Number: +33142385127; Email: nathalie.dhedin@aphp.fr
• Study Contact Backup: Name: Sylvie Chevret; Phone Number: +33142499742; Email: sylvie.chevret@paris7.jussieu.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

• SCD patients (SS/Sβ0)
• Aged :15 to 45 years
• With at least one non-SCD sibling > 18 years from the same parental couple
• Who presented at least one of the following criteria:
• 3 VOC requiring hospitalization over one year within the past 2 years and at least a past history of an ACS
• At least 1 ACS within the past 2 years requiring transfusions
• History of ischemic stroke or cerebral/cervical arterial stenosis > 50%
• Pulmonary hypertension defined by mean pulmonary artery pressure ≥ 25 mmHg at rest, determined by right heart catherization
• Requiring treatment with Hydroxyurea or chronic transfusion, or already treated by Hydroxyurea or transfusion program (TP) at inclusion.
• Patients already receiving chronic transfusions for VOC or ACS not responding to hydroxyurea, will be eligible, provided at least 3 VOC requiring hospitalization/year within the 2 years before initiation of chronic transfusions, and at least past history of an ACS.
• Contraception during all the study period by sirolimus for women of child bearing potential
• Signed informed consent
• Amenable to HLA typing, HSCT if an HLA-identical sibling is available.
• Patients affiliated to the French health care insurance

Exclusion Criteria

• Performance status: ECOG scale>1
• Pulmonary function: FEV1 et CVF < 50% of the theorical value
• Post capillary and severe pre-capillary pulmonary hypertension with measured mean pulmonary artery pressure at rest >35 mmHg
• Cardiac ejection fraction < 45%
• Estimated glomerular fraction rate (GFR) <50ml/mn /1.73m2
• Conjugate bilirubin >50 µmole/L, cirrhosis, ALT>4N
• Uncontrolled infection
• Known hypersensitivity of alemtuzumab
• Known hypersensitivity to murine proteins and to the following excepients: disodium edetate, polysorbate 80, potassium chloride, potassium phosphate monobasic, sodium chloride, dibasic sodium phosphate, water for injections
• Positivity for HIV
• Pregnancy or breast-feeding women
• Alloimmunization or Delayed Hemolytic Transfusion Reaction precluding red cell transfusions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HLA matched haematopoietic stem cell transplantation; Peripheral blood stem cell from matched HLA related donor.	Procedure: Allogeneic matched related haematopoietic stem cell transplantation; Allogeneic matched related haematopoietic stem cell transplantation after a reduced intensity conditioning regimen
Other: Control arm; Best standard care : Patients will receive the best standard care according to their situation and their previous treatment: initiation of Hydroxyurea, continuation or optimization of the dose of Hydroxyurea, initiation or continuation of TP, initiation of a new drug proved to improve SCD and having authorization to use in France.	Other: Standard arm; In the standard arm, patients who will not be transplanted, will receive the best standard care according to their situation and their previous treatment: initiation of hydroxyurea, continuation or optimization of the dose of hydroxyurea, initiation or continuation of transfusion program, initiation of a new drug proved to improve SCD and having authorization to use in France

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2 year event-free survival	An event will be defined as : death from any cause; or acute grade II-IV GVHD according to the Magic consortium 2016 classification or a moderate or severe chronic GVHD according to the NIH classification; or 3 hospitalizations for VOC defined according to usual criteria; or one ACS defined by usual clinical criteria and a pulmonary infiltrate on chest film and/or thoracic computed-tomography (CT) scan; or a stroke defined as a clinical event confirmed by an MRI; or a cerebral or cervical stenosis >25% in a new territory, or increase >25% of previous stenosis evaluated MRI and MRI; or a increased of at least +10% of tricuspid regurgitation velocity, (confirmed by 2 echocardiography performed with a delay of at least 3 months) compared with pre-inclusion value for patients with TRV≥2.7 at inclusion	2 years post-inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		2 years post-inclusion
Number of days requiring hospitalization	Number of days requiring hospitalization at 1 year post-inclusion with exclusion of the 5 first months post-inclusion	1 year
Number of days requiring hospitalization	Number of days requiring hospitalization at 2 years post-inclusion with exclusion of the 5 first months post-inclusion	2 years post-inclusion
Number of vaso-occlusive crisis (VOC) requiring hospitalization		1 year post-inclusion
Number of vaso-occlusive crisis (VOC) requiring hospitalization		2 years post-inclusion
Number of acute chest syndrome (ACS) requiring hospitalization		1 year post-inclusion
Number of acute chest syndrome (ACS) requiring hospitalization		2 years post-inclusion
Number of hospitalizations in intensive care unit		1 year post-inclusion
Number of hospitalizations in intensive care unit		2 years post-inclusion
Number of priapism		1 year post-inclusion
Number of priapism		2 years post-inclusion
Number of stroke episodes		1 year post-inclusion
Number of stroke episodes		2 years post-inclusion
LDH count	Changes in LDH	every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
Percentage of patients with an aminotransferase value higher than five times the normal value	Changes in aminotransferase	every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
Percentage of patients with a gamma-GT value higher than five times the normal value	Changes in gamma-GT	every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
Percentage of patients with an Alkaline phosphatase value higher than five times the normal value	Changes in alkaline phosphatase	every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
Percentage of patients with a bilirubin value higher than three times the normal value	Changes in bilirubin	every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
Percentage of patients with a prothrombin value less than 70%	Changes in TP	every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
Activated partial thromboplastin time higher than 1.5 times the normal value	Changes in TCK	every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
Rate of hemoglobin	Changes in hemoglobin level	every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
Hematocrit	Changes in hematocrit	every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
Mean corpuscular volume	Changes in mean corpuscular volume	every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
Hemoglobin variants	Changes of percentage of hemoglobin variants	every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
Reticulocyte count	Changes in percentage of reticulocyte	every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
White blood cells count	Changes in white blood cells	every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
Platelets counts	Changes in platelet counts	every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
Microalbuminuria/creatininuria ratio		at 3 months
Microalbuminuria/creatininuria ratio		at 6 months
Microalbuminuria/creatininuria ratio		at 12 months
Microalbuminuria/creatininuria ratio		at 24 months
Ferritin level		at 3 months
Ferritin level		at 6 months
Ferritin level		at 12 months
Ferritin level		at 24 months
Transferrin saturation level		at 3 months
Percentage of transferrin saturation		at 6 months
Percentage of transferrin saturation		at 12 months
Percentage of transferrin saturation		at 24 months
LH count	Gonadic function will be measured using LH	at 24 months
FSH count	Gonadic function will be measured using FSH	at 24 months
Testosterone count	Gonadic function will be measured using testosterone level in men	at 24 months
Spermogram	Gonadic function will be measured using spermogram in men	at 24 months
Oestrogen count	Gonadic function will be measured using oestrogen level in women	at 24 months
AMH count	Gonadic function will be measured using AMH level in women	at 24 months
Incidence of amenorrhea	Gonadic function will be measured using incidence of amenorrhea in women	at 24 months
Number of parity		at 24 months
Percentage of patients with a proliferative retinopathy	Changes in retinopathy status (appearance, disappearance, improvement, aggravation)	at 12 months
Percentage of patients with a proliferative retinopathy	Changes in retinopathy status (appearance, disappearance, improvement, aggravation)	at 24 months
Percentage of patients with a hemorrhagic retinopathy	Changes in retinopathy status (appearance, disappearance, improvement, aggravation)	at 12 months
Percentage of patients with a hemorrhagic retinopathy	Changes in retinopathy status (appearance, disappearance, improvement, aggravation)	at 24 months
Percentage of patients with retinal detachment	Changes in retinopathy status (appearance, disappearance, improvement, aggravation)	at 12 months
Percentage of patients with retinal detachment	Changes in retinopathy status (appearance, disappearance, improvement, aggravation)	at 24 months
Proportion of patients with keratitis	Changes in retinopathy status (appearance, disappearance, improvement, aggravation)	at 12 months
Proportion of patients with keratitis	Changes in retinopathy status (appearance, disappearance, improvement, aggravation)	at 24 months
Proportion of patients with uveitis	Changes in retinopathy status (appearance, disappearance, improvement, aggravation)	at 12 months
Proportion of patients with uveitis	Changes in retinopathy status (appearance, disappearance, improvement, aggravation)	at 24 months
Tricuspid regurgitant jet velocity	Heart function will be assessed by a transthoracic echocardiography and using tricuspid régurgitant jet velocity	at 12 months
Tricuspid regurgitant jet velocity	Heart function will be assessed by a transthoracic echocardiography and using tricuspid régurgitant jet velocity	at 24 months
Left atrial dimension	Heart function will be assessed by a transthoracic echocardiography using left atrial dimension indexed to body surface	at 12 months
Left atrial dimension	Heart function will be assessed by a transthoracic echocardiography using left atrial dimension indexed to body surface	at 24 months
Left ventricular dimension	Heart function will be assessed by a transthoracic echocardiography using left ventricular dimension indexed to body surface	at 12 months
Left ventricular dimension	Heart function will be assessed by a transthoracic echocardiography using left ventricular dimension indexed to body surface	at 24 months
Ventricular mass index value	Heart function will be assessed by a transthoracic echocardiography using ventricular mass index	at 12 months
Ventricular mass index value	Heart function will be assessed by a transthoracic echocardiography using ventricular mass index	at 24 months
Left ventricular ejection fraction	Heart function will be assessed by a transthoracic echocardiography using left ventricular ejection fraction	at 12 months
Left ventricular ejection fraction	Heart function will be assessed by a transthoracic echocardiography using left ventricular ejection fraction	at 24 months
Forced Expiratory Volume in one second (FEV)	Lung function will be evaluated Forced Expiratory Volume in one second (FEV) , %	at 12 months
Forced Expiratory Volume in one second (FEV)	Lung function will be evaluated Forced Expiratory Volume in one second (FEV) , %	at 24 months
DLCO	Lung function will be evaluated using DLCO the diffusion capacity of carbon monoxide	at 12 months
DLCO	Lung function will be evaluated using DLCO the diffusion capacity of carbon monoxide	at 24 months
Forced vital capacity	Lung function will be evaluated using forced vital capacity (FVC)	at 12 months
Forced vital capacity	Lung function will be evaluated using forced vital capacity (FVC)	at 24 months
6 minutes walk test	Lung function will be evaluated using 6 minutes walk test	at 12 months
6 minutes walk test	Lung function will be evaluated using 6 minutes walk test	at 24 months
Number of new episodes of avascular osteonecrosis		at 24 months
Number of patients for each location of new episodes of avascular osteonecrosis	Location of new episodes of avascular osteonecrosis will be assessed using radiography and magnetic resonance imaging	at 24 months
Fractures	Number of new episodes of fractures	at 24 months
Central nervous system function	Central nervous system function will be assessed using magnetic resonance Imaging with ARM/MRI	at 12 months
Central nervous system function	Central nervous system function will be assessed using magnetic resonance Imaging with ARM/MRI	at 24 months
Iron overload	Iron overload will be assessed using liver and heart magnetic resonance Imaging in patients with ferritin > 1000 microg/L	at inclusion
Iron overload	Iron overload will be assessed using liver and heart magnetic resonance Imaging in patients with ferritin > 1000 microg/L	at 12 months
Iron overload	Iron overload will be assessed using liver and heart magnetic resonance Imaging in patients with ferritin > 1000 microg/L	at 24 months
Red blood cell packed transfused	Number of red blood cell packed transfused from 6 months post-inclusion (pre and early post-transplant transfusion are a standard of care and may not be counted)	at 24 months
Number of delayed hemolytic transfusion reaction (DHTR)	DHTR will be defined as associated with hemoglobinuria/dark urine in the month following transfusion +/- bone pain with increased hemolytic markers and drop in HbA or new RBC allo-Ab	at 3 months
Number of delayed hemolytic transfusion reaction (DHTR)	DHTR will be defined as associated with hemoglobinuria/dark urine in the month following transfusion +/- bone pain with increased hemolytic markers and drop in HbA or new RBC allo-Ab	at 6 months
Number of delayed hemolytic transfusion reaction (DHTR)	DHTR will be defined as associated with hemoglobinuria/dark urine in the month following transfusion +/- bone pain with increased hemolytic markers and drop in HbA or new RBC allo-Ab	at 12 months
Number of delayed hemolytic transfusion reaction (DHTR)	DHTR will be defined as associated with hemoglobinuria/dark urine in the month following transfusion +/- bone pain with increased hemolytic markers and drop in HbA or new RBC allo-Ab	at 24 months
Proportion of patients with new RBC alloantibodies	New RBC alloantibodies will be assessed using blood test	at 3 months
Proportion of patients with new RBC alloantibodies	New RBC alloantibodies will be assessed using blood test	at 6 months
Proportion of patients with new RBC alloantibodies	New RBC alloantibodies will be assessed using blood test	at 12 months
Proportion of patients with new RBC alloantibodies	New RBC alloantibodies will be assessed using blood test	at 24 months
Percentage of patients with an oral opioid consumption		at 3 months
Percentage of patients with an oral opioid consumption		at 6 months
Percentage of patients with an oral opioid consumption		at 12 months
Percentage of patients with an oral opioid consumption		at 24 months
Quality of life evaluated using MOS SF36 questionnaire	Quality of life evaluated using MOS SF36 questionnaire (Medical Outcomes Study - 36-Item Short Form Health Survey). SF-36 is a set of generic, coherent, and easily administered quality-of-life measures. These measures rely upon patient self-reporting. Items are grouped into three categories: functional status, well-being, overall health assessment. In two dimensions, the answer is binary (yes / no) and in the other 6 in ordinal quality (3 to 6 possible answers). For each dimension, the scores for the different items are coded and then summed and transformed linearly on a scale ranging from 0 to 100. A physical composite score and a mental composite score can be calculated according to an established algorithm	at 3 months
Quality of life evaluated using MOS SF36 questionnaire	Quality of life evaluated using MOS SF36 questionnaire (Medical Outcomes Study - 36-Item Short Form Health Survey). SF-36 is a set of generic, coherent, and easily administered quality-of-life measures. These measures rely upon patient self-reporting. Items are grouped into three categories: functional status, well-being, overall health assessment. In two dimensions, the answer is binary (yes / no) and in the other 6 in ordinal quality (3 to 6 possible answers). For each dimension, the scores for the different items are coded and then summed and transformed linearly on a scale ranging from 0 to 100. A physical composite score and a mental composite score can be calculated according to an established algorithm	at 6 months
Quality of life evaluated using MOS SF36 questionnaire	Quality of life evaluated using MOS SF36 questionnaire (Medical Outcomes Study - 36-Item Short Form Health Survey). SF-36 is a set of generic, coherent, and easily administered quality-of-life measures. These measures rely upon patient self-reporting. Items are grouped into three categories: functional status, well-being, overall health assessment. In two dimensions, the answer is binary (yes / no) and in the other 6 in ordinal quality (3 to 6 possible answers). For each dimension, the scores for the different items are coded and then summed and transformed linearly on a scale ranging from 0 to 100. A physical composite score and a mental composite score can be calculated according to an established algorithm	at 12 months
Quality of life evaluated using MOS SF36 questionnaire	Quality of life evaluated using MOS SF36 questionnaire (Medical Outcomes Study - 36-Item Short Form Health Survey). SF-36 is a set of generic, coherent, and easily administered quality-of-life measures. These measures rely upon patient self-reporting. Items are grouped into three categories: functional status, well-being, overall health assessment. In two dimensions, the answer is binary (yes / no) and in the other 6 in ordinal quality (3 to 6 possible answers). For each dimension, the scores for the different items are coded and then summed and transformed linearly on a scale ranging from 0 to 100. A physical composite score and a mental composite score can be calculated according to an established algorithm	at 24 months
Depression and Anxiety status	Depression and anxiety will be assessed using Hospital Anxiety and Depression Scale (HADS) questionnaire. The HAD scale is a self-assessment scale for detecting states of depression and anxiety in the setting of an hospital medical outpatient clinic. HADS is a self-administered scale of 14 items which assessed levels of depression and anxiety, divided into 2 subscales of 7 items (Anxiety or HADS-A, Depression or HADS-D). Each item is scored on a scale of 0 to 3. A score is generated for each of the two sub-scales (sum of the 7 items, ranging from 0 to 21). Limit scores, for each of the scores, distinguish: non-cases or asymptomatic ones (score ≤ 7); probable or borderline cases (score 8-10); clearly or clinically symptomatic cases (score ≥ 11).	at 3 months
Depression and Anxiety status	HADS is a self-administered scale of 14 items which assessed levels of depression and anxiety, divided into 2 subscales of 7 items (Anxiety or HADS-A, Depression or HADS-D). Each item is scored on a scale of 0 to 3. A score is generated for each of the two sub-scales (sum of the 7 items, ranging from 0 to 21). Limit scores, for each of the scores, distinguish: non-cases or asymptomatic ones (score ≤ 7); probable or borderline cases (score 8-10); clearly or clinically symptomatic cases (score ≥ 11).	at 6 months
Depression and Anxiety status	Depression and anxiety will be assessed using Hospital Anxiety and Depression Scale (HADS) questionnaire. The HAD scale is a self-assessment scale for detecting states of depression and anxiety in the setting of an hospital medical outpatient clinic. HADS is a self-administered scale of 14 items which assessed levels of depression and anxiety, divided into 2 subscales of 7 items (Anxiety or HADS-A, Depression or HADS-D). Each item is scored on a scale of 0 to 3. A score is generated for each of the two sub-scales (sum of the 7 items, ranging from 0 to 21). Limit scores, for each of the scores, distinguish: non-cases or asymptomatic ones (score ≤ 7); probable or borderline cases (score 8-10); clearly or clinically symptomatic cases (score ≥ 11).	at 12 months
Weight	Evolution of weight	at 3 months
Weight	Evolution of weight	at 6 months
Weight	Evolution of weight	at 12 months
Weight	Evolution of weight	at 24 months
Number of severe infections	A severe infection will be defined as a CTAE score of grade 3 or 4	at 24 months
GvHD incidence		at 12 months
GvHD incidence		at 24 months
Grading of GvHD	Grading of GvHD will be assessed using magic consortium 2016 and NIH classification	at 12 months
Chimerism in HSCT	Chimerism in HSCT will be assessed on total blood population and on T subset. In patients transplanted in Paris area, a more extensive centralized chimerism will be performed if donor T lymphocyte chimerism will be under 70% at 3 months post-transplant. Chimerism analysis by PCR microsatellite or by quantitative real-time PCR of insertion/deletion	at 1 month
Chimerism in HSCT	Chimerism in HSCT will be assessed on total blood population and on T subset. In patients transplanted in Paris area, a more extensive centralized chimerism will be performed if donor T lymphocyte chimerism will be under 70% at 3 months post-transplant. Chimerism analysis by PCR microsatellite or by quantitative real-time PCR of insertion/deletion	at 2 months
Chimerism in HSCT	Chimerism in HSCT will be assessed on total blood population and on T subset. In patients transplanted in Paris area, a more extensive centralized chimerism will be performed if donor T lymphocyte chimerism will be under 70% at 3 months post-transplant. Chimerism analysis by PCR microsatellite or by quantitative real-time PCR of insertion/deletion	at 3 months
Chimerism in HSCT	Chimerism in HSCT will be assessed on total blood population and on T subset. In patients transplanted in Paris area, a more extensive centralized chimerism will be performed if donor T lymphocyte chimerism will be under 70% at 3 months post-transplant. Chimerism analysis by PCR microsatellite or by quantitative real-time PCR of insertion/deletionchimerism will be performed if donor T lymphocyte chimerism will be under 70% at 3 months post-transplant.	at 6 months
Chimerism in HSCT	Chimerism in HSCT will be assessed on total blood population and on T subset. In patients transplanted in Paris area, a more extensive centralized chimerism will be performed if donor T lymphocyte chimerism will be under 70% at 3 months post-transplant. Chimerism analysis by PCR microsatellite or by quantitative real-time PCR of insertion/deletion	at 9 months
Chimerism in HSCT	Chimerism in HSCT will be assessed on total blood population and on T subset. In patients transplanted in Paris area, a more extensive centralized chimerism will be performed if donor T lymphocyte chimerism will be under 70% at 3 months post-transplant. Chimerism analysis by PCR microsatellite or by quantitative real-time PCR of insertion/deletion	at 12 months
Chimerism in HSCT	Chimerism in HSCT will be assessed on total blood population and on T subset. In patients transplanted in Paris area, a more extensive centralized chimerism will be performed if donor T lymphocyte chimerism will be under 70% at 3 months post-transplant. Chimerism analysis by PCR microsatellite or by quantitative real-time PCR of insertion/deletion	at 18 months
Chimerism in HSCT	Chimerism in HSCT will be assessed on total blood population and on T subset. In patients transplanted in Paris area, a more extensive centralized chimerism will be performed if donor T lymphocyte chimerism will be under 70% at 3 months post-transplant. Chimerism analysis by PCR microsatellite or by quantitative real-time PCR of insertion/deletion	at 24 months
Number of days of hospitalization	Number of days of hospitalization from inclusion	Number of days of hospitalization from inclusion at M24
RBC and WBC adherence	Study of RBC and WBC adherence on lymphocytes subpopulation (including NK-T cells). Modulation of WBC and RBC surface markers by allograft.	at inclusion
RBC and WBC adherence	Study of RBC and WBC adherence on lymphocytes subpopulation (including NK-T cells). Modulation of WBC and RBC surface markers by allograft.	at 12 months
RBC and WBC adherence	Study of RBC and WBC adherence on lymphocytes subpopulation (including NK-T cells). Modulation of WBC and RBC surface markers by allograft.	at 24 months
Expression of RBC and WBC surface markers	Expression of RBC and WBC surface markers on lymphocytes subpopulation	at inclusion
Expression of RBC and WBC surface markers	Expression of RBC and WBC surface markers on lymphocytes subpopulation	at 12 months
Expression of RBC and WBC surface markers	Expression of RBC and WBC surface markers on lymphocytes subpopulation	at 24 months
Mast cell mediator release	Master cell mediator release will be assessed using plasma sample. Modulation of mast cell mediators release by allograft (tryptase, substance P and histamine)	at inclusion
Mast cell mediator release	Master cell mediator release will be assessed using plasma sample. Modulation of mast cell mediators release by allograft (tryptase, substance P and histamine)	at 12 months
Mast cell mediator release	Master cell mediator release will be assessed using plasma sample. Modulation of mast cell mediators release by allograft (tryptase, substance P and histamine)	at 24 months
Inflammatory cytokines	Inflammatory cytokines will be measured using serum sample. Modulation of inflammatory cytokine (TNF-alpha, IL-1, IL-6...) by allograft	at inclusion
Inflammatory cytokines	Inflammatory cytokines will be measured using serum sample. Modulation of inflammatory cytokine (TNF-alpha, IL-1, IL-6...) by allograft	at 12 months
Inflammatory cytokines	Inflammatory cytokines will be measured using serum sample. Modulation of inflammatory cytokine (TNF-alpha, IL-1, IL-6...) by allograft	at 24 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Anticipated): October 15, 2019
• Primary Completion (Anticipated): October 15, 2024
• Study Completion (Anticipated): October 15, 2024

Study Registration Dates

• First Submitted: July 15, 2019
• First Submitted That Met QC Criteria: August 2, 2019
• First Posted (Actual): August 6, 2019

Study Record Updates

• Last Update Posted (Actual): September 23, 2019
• Last Update Submitted That Met QC Criteria: September 20, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: K170912J

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No