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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)

Primary Purpose

Sickle Cell Disease

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Allogeneic matched related haematopoietic stem cell transplantation
Standard arm
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Disease

Eligibility Criteria

15 Years - 45 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Other

    Arm Label

    HLA matched haematopoietic stem cell transplantation

    Control arm

    Arm Description

    Peripheral blood stem cell from matched HLA related donor.

    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.

    Outcomes

    Primary Outcome Measures

    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

    Secondary Outcome Measures

    Overall survival
    Number of days requiring hospitalization
    Number of days requiring hospitalization at 1 year post-inclusion with exclusion of the 5 first months post-inclusion
    Number of days requiring hospitalization
    Number of days requiring hospitalization at 2 years post-inclusion with exclusion of the 5 first months post-inclusion
    Number of vaso-occlusive crisis (VOC) requiring hospitalization
    Number of vaso-occlusive crisis (VOC) requiring hospitalization
    Number of acute chest syndrome (ACS) requiring hospitalization
    Number of acute chest syndrome (ACS) requiring hospitalization
    Number of hospitalizations in intensive care unit
    Number of hospitalizations in intensive care unit
    Number of priapism
    Number of priapism
    Number of stroke episodes
    Number of stroke episodes
    LDH count
    Changes in LDH
    Percentage of patients with an aminotransferase value higher than five times the normal value
    Changes in aminotransferase
    Percentage of patients with a gamma-GT value higher than five times the normal value
    Changes in gamma-GT
    Percentage of patients with an Alkaline phosphatase value higher than five times the normal value
    Changes in alkaline phosphatase
    Percentage of patients with a bilirubin value higher than three times the normal value
    Changes in bilirubin
    Percentage of patients with a prothrombin value less than 70%
    Changes in TP
    Activated partial thromboplastin time higher than 1.5 times the normal value
    Changes in TCK
    Rate of hemoglobin
    Changes in hemoglobin level
    Hematocrit
    Changes in hematocrit
    Mean corpuscular volume
    Changes in mean corpuscular volume
    Hemoglobin variants
    Changes of percentage of hemoglobin variants
    Reticulocyte count
    Changes in percentage of reticulocyte
    White blood cells count
    Changes in white blood cells
    Platelets counts
    Changes in platelet counts
    Microalbuminuria/creatininuria ratio
    Microalbuminuria/creatininuria ratio
    Microalbuminuria/creatininuria ratio
    Microalbuminuria/creatininuria ratio
    Ferritin level
    Ferritin level
    Ferritin level
    Ferritin level
    Transferrin saturation level
    Percentage of transferrin saturation
    Percentage of transferrin saturation
    Percentage of transferrin saturation
    LH count
    Gonadic function will be measured using LH
    FSH count
    Gonadic function will be measured using FSH
    Testosterone count
    Gonadic function will be measured using testosterone level in men
    Spermogram
    Gonadic function will be measured using spermogram in men
    Oestrogen count
    Gonadic function will be measured using oestrogen level in women
    AMH count
    Gonadic function will be measured using AMH level in women
    Incidence of amenorrhea
    Gonadic function will be measured using incidence of amenorrhea in women
    Number of parity
    Percentage of patients with a proliferative retinopathy
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Percentage of patients with a proliferative retinopathy
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Percentage of patients with a hemorrhagic retinopathy
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Percentage of patients with a hemorrhagic retinopathy
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Percentage of patients with retinal detachment
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Percentage of patients with retinal detachment
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Proportion of patients with keratitis
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Proportion of patients with keratitis
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Proportion of patients with uveitis
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Proportion of patients with uveitis
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Tricuspid regurgitant jet velocity
    Heart function will be assessed by a transthoracic echocardiography and using tricuspid régurgitant jet velocity
    Tricuspid regurgitant jet velocity
    Heart function will be assessed by a transthoracic echocardiography and using tricuspid régurgitant jet velocity
    Left atrial dimension
    Heart function will be assessed by a transthoracic echocardiography using left atrial dimension indexed to body surface
    Left atrial dimension
    Heart function will be assessed by a transthoracic echocardiography using left atrial dimension indexed to body surface
    Left ventricular dimension
    Heart function will be assessed by a transthoracic echocardiography using left ventricular dimension indexed to body surface
    Left ventricular dimension
    Heart function will be assessed by a transthoracic echocardiography using left ventricular dimension indexed to body surface
    Ventricular mass index value
    Heart function will be assessed by a transthoracic echocardiography using ventricular mass index
    Ventricular mass index value
    Heart function will be assessed by a transthoracic echocardiography using ventricular mass index
    Left ventricular ejection fraction
    Heart function will be assessed by a transthoracic echocardiography using left ventricular ejection fraction
    Left ventricular ejection fraction
    Heart function will be assessed by a transthoracic echocardiography using left ventricular ejection fraction
    Forced Expiratory Volume in one second (FEV)
    Lung function will be evaluated Forced Expiratory Volume in one second (FEV) , %
    Forced Expiratory Volume in one second (FEV)
    Lung function will be evaluated Forced Expiratory Volume in one second (FEV) , %
    DLCO
    Lung function will be evaluated using DLCO the diffusion capacity of carbon monoxide
    DLCO
    Lung function will be evaluated using DLCO the diffusion capacity of carbon monoxide
    Forced vital capacity
    Lung function will be evaluated using forced vital capacity (FVC)
    Forced vital capacity
    Lung function will be evaluated using forced vital capacity (FVC)
    6 minutes walk test
    Lung function will be evaluated using 6 minutes walk test
    6 minutes walk test
    Lung function will be evaluated using 6 minutes walk test
    Number of new episodes of avascular osteonecrosis
    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
    Fractures
    Number of new episodes of fractures
    Central nervous system function
    Central nervous system function will be assessed using magnetic resonance Imaging with ARM/MRI
    Central nervous system function
    Central nervous system function will be assessed using magnetic resonance Imaging with ARM/MRI
    Iron overload
    Iron overload will be assessed using liver and heart magnetic resonance Imaging in patients with ferritin > 1000 microg/L
    Iron overload
    Iron overload will be assessed using liver and heart magnetic resonance Imaging in patients with ferritin > 1000 microg/L
    Iron overload
    Iron overload will be assessed using liver and heart magnetic resonance Imaging in patients with ferritin > 1000 microg/L
    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)
    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
    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
    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
    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
    Proportion of patients with new RBC alloantibodies
    New RBC alloantibodies will be assessed using blood test
    Proportion of patients with new RBC alloantibodies
    New RBC alloantibodies will be assessed using blood test
    Proportion of patients with new RBC alloantibodies
    New RBC alloantibodies will be assessed using blood test
    Proportion of patients with new RBC alloantibodies
    New RBC alloantibodies will be assessed using blood test
    Percentage of patients with an oral opioid consumption
    Percentage of patients with an oral opioid consumption
    Percentage of patients with an oral opioid consumption
    Percentage of patients with an oral opioid consumption
    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
    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
    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
    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
    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).
    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).
    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).
    Weight
    Evolution of weight
    Weight
    Evolution of weight
    Weight
    Evolution of weight
    Weight
    Evolution of weight
    Number of severe infections
    A severe infection will be defined as a CTAE score of grade 3 or 4
    GvHD incidence
    GvHD incidence
    Grading of GvHD
    Grading of GvHD will be assessed using magic consortium 2016 and NIH classification
    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
    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
    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
    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.
    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
    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
    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
    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
    Number of days of hospitalization
    Number of days of hospitalization from 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.
    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.
    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.
    Expression of RBC and WBC surface markers
    Expression of RBC and WBC surface markers on lymphocytes subpopulation
    Expression of RBC and WBC surface markers
    Expression of RBC and WBC surface markers on lymphocytes subpopulation
    Expression of RBC and WBC surface markers
    Expression of RBC and WBC surface markers on lymphocytes subpopulation
    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)
    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)
    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)
    Inflammatory cytokines
    Inflammatory cytokines will be measured using serum sample. Modulation of inflammatory cytokine (TNF-alpha, IL-1, IL-6...) by allograft
    Inflammatory cytokines
    Inflammatory cytokines will be measured using serum sample. Modulation of inflammatory cytokine (TNF-alpha, IL-1, IL-6...) by allograft
    Inflammatory cytokines
    Inflammatory cytokines will be measured using serum sample. Modulation of inflammatory cytokine (TNF-alpha, IL-1, IL-6...) by allograft

    Full Information

    First Posted
    July 15, 2019
    Last Updated
    September 20, 2019
    Sponsor
    Assistance Publique - Hôpitaux de Paris
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04046705
    Brief Title
    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
    Acronym
    DREPA-RIC
    Official Title
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2019
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 15, 2019 (Anticipated)
    Primary Completion Date
    October 15, 2024 (Anticipated)
    Study Completion Date
    October 15, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Assistance Publique - Hôpitaux de Paris

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Sickle Cell Disease

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    78 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    HLA matched haematopoietic stem cell transplantation
    Arm Type
    Experimental
    Arm Description
    Peripheral blood stem cell from matched HLA related donor.
    Arm Title
    Control arm
    Arm Type
    Other
    Arm Description
    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.
    Intervention Type
    Procedure
    Intervention Name(s)
    Allogeneic matched related haematopoietic stem cell transplantation
    Intervention Description
    Allogeneic matched related haematopoietic stem cell transplantation after a reduced intensity conditioning regimen
    Intervention Type
    Other
    Intervention Name(s)
    Standard arm
    Intervention Description
    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
    Primary Outcome Measure Information:
    Title
    2 year event-free survival
    Description
    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
    Time Frame
    2 years post-inclusion
    Secondary Outcome Measure Information:
    Title
    Overall survival
    Time Frame
    2 years post-inclusion
    Title
    Number of days requiring hospitalization
    Description
    Number of days requiring hospitalization at 1 year post-inclusion with exclusion of the 5 first months post-inclusion
    Time Frame
    1 year
    Title
    Number of days requiring hospitalization
    Description
    Number of days requiring hospitalization at 2 years post-inclusion with exclusion of the 5 first months post-inclusion
    Time Frame
    2 years post-inclusion
    Title
    Number of vaso-occlusive crisis (VOC) requiring hospitalization
    Time Frame
    1 year post-inclusion
    Title
    Number of vaso-occlusive crisis (VOC) requiring hospitalization
    Time Frame
    2 years post-inclusion
    Title
    Number of acute chest syndrome (ACS) requiring hospitalization
    Time Frame
    1 year post-inclusion
    Title
    Number of acute chest syndrome (ACS) requiring hospitalization
    Time Frame
    2 years post-inclusion
    Title
    Number of hospitalizations in intensive care unit
    Time Frame
    1 year post-inclusion
    Title
    Number of hospitalizations in intensive care unit
    Time Frame
    2 years post-inclusion
    Title
    Number of priapism
    Time Frame
    1 year post-inclusion
    Title
    Number of priapism
    Time Frame
    2 years post-inclusion
    Title
    Number of stroke episodes
    Time Frame
    1 year post-inclusion
    Title
    Number of stroke episodes
    Time Frame
    2 years post-inclusion
    Title
    LDH count
    Description
    Changes in LDH
    Time Frame
    every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
    Title
    Percentage of patients with an aminotransferase value higher than five times the normal value
    Description
    Changes in aminotransferase
    Time Frame
    every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
    Title
    Percentage of patients with a gamma-GT value higher than five times the normal value
    Description
    Changes in gamma-GT
    Time Frame
    every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
    Title
    Percentage of patients with an Alkaline phosphatase value higher than five times the normal value
    Description
    Changes in alkaline phosphatase
    Time Frame
    every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
    Title
    Percentage of patients with a bilirubin value higher than three times the normal value
    Description
    Changes in bilirubin
    Time Frame
    every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
    Title
    Percentage of patients with a prothrombin value less than 70%
    Description
    Changes in TP
    Time Frame
    every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
    Title
    Activated partial thromboplastin time higher than 1.5 times the normal value
    Description
    Changes in TCK
    Time Frame
    every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
    Title
    Rate of hemoglobin
    Description
    Changes in hemoglobin level
    Time Frame
    every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
    Title
    Hematocrit
    Description
    Changes in hematocrit
    Time Frame
    every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
    Title
    Mean corpuscular volume
    Description
    Changes in mean corpuscular volume
    Time Frame
    every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
    Title
    Hemoglobin variants
    Description
    Changes of percentage of hemoglobin variants
    Time Frame
    every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
    Title
    Reticulocyte count
    Description
    Changes in percentage of reticulocyte
    Time Frame
    every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
    Title
    White blood cells count
    Description
    Changes in white blood cells
    Time Frame
    every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
    Title
    Platelets counts
    Description
    Changes in platelet counts
    Time Frame
    every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm
    Title
    Microalbuminuria/creatininuria ratio
    Time Frame
    at 3 months
    Title
    Microalbuminuria/creatininuria ratio
    Time Frame
    at 6 months
    Title
    Microalbuminuria/creatininuria ratio
    Time Frame
    at 12 months
    Title
    Microalbuminuria/creatininuria ratio
    Time Frame
    at 24 months
    Title
    Ferritin level
    Time Frame
    at 3 months
    Title
    Ferritin level
    Time Frame
    at 6 months
    Title
    Ferritin level
    Time Frame
    at 12 months
    Title
    Ferritin level
    Time Frame
    at 24 months
    Title
    Transferrin saturation level
    Time Frame
    at 3 months
    Title
    Percentage of transferrin saturation
    Time Frame
    at 6 months
    Title
    Percentage of transferrin saturation
    Time Frame
    at 12 months
    Title
    Percentage of transferrin saturation
    Time Frame
    at 24 months
    Title
    LH count
    Description
    Gonadic function will be measured using LH
    Time Frame
    at 24 months
    Title
    FSH count
    Description
    Gonadic function will be measured using FSH
    Time Frame
    at 24 months
    Title
    Testosterone count
    Description
    Gonadic function will be measured using testosterone level in men
    Time Frame
    at 24 months
    Title
    Spermogram
    Description
    Gonadic function will be measured using spermogram in men
    Time Frame
    at 24 months
    Title
    Oestrogen count
    Description
    Gonadic function will be measured using oestrogen level in women
    Time Frame
    at 24 months
    Title
    AMH count
    Description
    Gonadic function will be measured using AMH level in women
    Time Frame
    at 24 months
    Title
    Incidence of amenorrhea
    Description
    Gonadic function will be measured using incidence of amenorrhea in women
    Time Frame
    at 24 months
    Title
    Number of parity
    Time Frame
    at 24 months
    Title
    Percentage of patients with a proliferative retinopathy
    Description
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Time Frame
    at 12 months
    Title
    Percentage of patients with a proliferative retinopathy
    Description
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Time Frame
    at 24 months
    Title
    Percentage of patients with a hemorrhagic retinopathy
    Description
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Time Frame
    at 12 months
    Title
    Percentage of patients with a hemorrhagic retinopathy
    Description
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Time Frame
    at 24 months
    Title
    Percentage of patients with retinal detachment
    Description
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Time Frame
    at 12 months
    Title
    Percentage of patients with retinal detachment
    Description
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Time Frame
    at 24 months
    Title
    Proportion of patients with keratitis
    Description
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Time Frame
    at 12 months
    Title
    Proportion of patients with keratitis
    Description
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Time Frame
    at 24 months
    Title
    Proportion of patients with uveitis
    Description
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Time Frame
    at 12 months
    Title
    Proportion of patients with uveitis
    Description
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)
    Time Frame
    at 24 months
    Title
    Tricuspid regurgitant jet velocity
    Description
    Heart function will be assessed by a transthoracic echocardiography and using tricuspid régurgitant jet velocity
    Time Frame
    at 12 months
    Title
    Tricuspid regurgitant jet velocity
    Description
    Heart function will be assessed by a transthoracic echocardiography and using tricuspid régurgitant jet velocity
    Time Frame
    at 24 months
    Title
    Left atrial dimension
    Description
    Heart function will be assessed by a transthoracic echocardiography using left atrial dimension indexed to body surface
    Time Frame
    at 12 months
    Title
    Left atrial dimension
    Description
    Heart function will be assessed by a transthoracic echocardiography using left atrial dimension indexed to body surface
    Time Frame
    at 24 months
    Title
    Left ventricular dimension
    Description
    Heart function will be assessed by a transthoracic echocardiography using left ventricular dimension indexed to body surface
    Time Frame
    at 12 months
    Title
    Left ventricular dimension
    Description
    Heart function will be assessed by a transthoracic echocardiography using left ventricular dimension indexed to body surface
    Time Frame
    at 24 months
    Title
    Ventricular mass index value
    Description
    Heart function will be assessed by a transthoracic echocardiography using ventricular mass index
    Time Frame
    at 12 months
    Title
    Ventricular mass index value
    Description
    Heart function will be assessed by a transthoracic echocardiography using ventricular mass index
    Time Frame
    at 24 months
    Title
    Left ventricular ejection fraction
    Description
    Heart function will be assessed by a transthoracic echocardiography using left ventricular ejection fraction
    Time Frame
    at 12 months
    Title
    Left ventricular ejection fraction
    Description
    Heart function will be assessed by a transthoracic echocardiography using left ventricular ejection fraction
    Time Frame
    at 24 months
    Title
    Forced Expiratory Volume in one second (FEV)
    Description
    Lung function will be evaluated Forced Expiratory Volume in one second (FEV) , %
    Time Frame
    at 12 months
    Title
    Forced Expiratory Volume in one second (FEV)
    Description
    Lung function will be evaluated Forced Expiratory Volume in one second (FEV) , %
    Time Frame
    at 24 months
    Title
    DLCO
    Description
    Lung function will be evaluated using DLCO the diffusion capacity of carbon monoxide
    Time Frame
    at 12 months
    Title
    DLCO
    Description
    Lung function will be evaluated using DLCO the diffusion capacity of carbon monoxide
    Time Frame
    at 24 months
    Title
    Forced vital capacity
    Description
    Lung function will be evaluated using forced vital capacity (FVC)
    Time Frame
    at 12 months
    Title
    Forced vital capacity
    Description
    Lung function will be evaluated using forced vital capacity (FVC)
    Time Frame
    at 24 months
    Title
    6 minutes walk test
    Description
    Lung function will be evaluated using 6 minutes walk test
    Time Frame
    at 12 months
    Title
    6 minutes walk test
    Description
    Lung function will be evaluated using 6 minutes walk test
    Time Frame
    at 24 months
    Title
    Number of new episodes of avascular osteonecrosis
    Time Frame
    at 24 months
    Title
    Number of patients for each location of new episodes of avascular osteonecrosis
    Description
    Location of new episodes of avascular osteonecrosis will be assessed using radiography and magnetic resonance imaging
    Time Frame
    at 24 months
    Title
    Fractures
    Description
    Number of new episodes of fractures
    Time Frame
    at 24 months
    Title
    Central nervous system function
    Description
    Central nervous system function will be assessed using magnetic resonance Imaging with ARM/MRI
    Time Frame
    at 12 months
    Title
    Central nervous system function
    Description
    Central nervous system function will be assessed using magnetic resonance Imaging with ARM/MRI
    Time Frame
    at 24 months
    Title
    Iron overload
    Description
    Iron overload will be assessed using liver and heart magnetic resonance Imaging in patients with ferritin > 1000 microg/L
    Time Frame
    at inclusion
    Title
    Iron overload
    Description
    Iron overload will be assessed using liver and heart magnetic resonance Imaging in patients with ferritin > 1000 microg/L
    Time Frame
    at 12 months
    Title
    Iron overload
    Description
    Iron overload will be assessed using liver and heart magnetic resonance Imaging in patients with ferritin > 1000 microg/L
    Time Frame
    at 24 months
    Title
    Red blood cell packed transfused
    Description
    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)
    Time Frame
    at 24 months
    Title
    Number of delayed hemolytic transfusion reaction (DHTR)
    Description
    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
    Time Frame
    at 3 months
    Title
    Number of delayed hemolytic transfusion reaction (DHTR)
    Description
    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
    Time Frame
    at 6 months
    Title
    Number of delayed hemolytic transfusion reaction (DHTR)
    Description
    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
    Time Frame
    at 12 months
    Title
    Number of delayed hemolytic transfusion reaction (DHTR)
    Description
    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
    Time Frame
    at 24 months
    Title
    Proportion of patients with new RBC alloantibodies
    Description
    New RBC alloantibodies will be assessed using blood test
    Time Frame
    at 3 months
    Title
    Proportion of patients with new RBC alloantibodies
    Description
    New RBC alloantibodies will be assessed using blood test
    Time Frame
    at 6 months
    Title
    Proportion of patients with new RBC alloantibodies
    Description
    New RBC alloantibodies will be assessed using blood test
    Time Frame
    at 12 months
    Title
    Proportion of patients with new RBC alloantibodies
    Description
    New RBC alloantibodies will be assessed using blood test
    Time Frame
    at 24 months
    Title
    Percentage of patients with an oral opioid consumption
    Time Frame
    at 3 months
    Title
    Percentage of patients with an oral opioid consumption
    Time Frame
    at 6 months
    Title
    Percentage of patients with an oral opioid consumption
    Time Frame
    at 12 months
    Title
    Percentage of patients with an oral opioid consumption
    Time Frame
    at 24 months
    Title
    Quality of life evaluated using MOS SF36 questionnaire
    Description
    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
    Time Frame
    at 3 months
    Title
    Quality of life evaluated using MOS SF36 questionnaire
    Description
    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
    Time Frame
    at 6 months
    Title
    Quality of life evaluated using MOS SF36 questionnaire
    Description
    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
    Time Frame
    at 12 months
    Title
    Quality of life evaluated using MOS SF36 questionnaire
    Description
    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
    Time Frame
    at 24 months
    Title
    Depression and Anxiety status
    Description
    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).
    Time Frame
    at 3 months
    Title
    Depression and Anxiety status
    Description
    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).
    Time Frame
    at 6 months
    Title
    Depression and Anxiety status
    Description
    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).
    Time Frame
    at 12 months
    Title
    Weight
    Description
    Evolution of weight
    Time Frame
    at 3 months
    Title
    Weight
    Description
    Evolution of weight
    Time Frame
    at 6 months
    Title
    Weight
    Description
    Evolution of weight
    Time Frame
    at 12 months
    Title
    Weight
    Description
    Evolution of weight
    Time Frame
    at 24 months
    Title
    Number of severe infections
    Description
    A severe infection will be defined as a CTAE score of grade 3 or 4
    Time Frame
    at 24 months
    Title
    GvHD incidence
    Time Frame
    at 12 months
    Title
    GvHD incidence
    Time Frame
    at 24 months
    Title
    Grading of GvHD
    Description
    Grading of GvHD will be assessed using magic consortium 2016 and NIH classification
    Time Frame
    at 12 months
    Title
    Chimerism in HSCT
    Description
    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
    Time Frame
    at 1 month
    Title
    Chimerism in HSCT
    Description
    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
    Time Frame
    at 2 months
    Title
    Chimerism in HSCT
    Description
    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
    Time Frame
    at 3 months
    Title
    Chimerism in HSCT
    Description
    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.
    Time Frame
    at 6 months
    Title
    Chimerism in HSCT
    Description
    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
    Time Frame
    at 9 months
    Title
    Chimerism in HSCT
    Description
    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
    Time Frame
    at 12 months
    Title
    Chimerism in HSCT
    Description
    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
    Time Frame
    at 18 months
    Title
    Chimerism in HSCT
    Description
    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
    Time Frame
    at 24 months
    Title
    Number of days of hospitalization
    Description
    Number of days of hospitalization from inclusion
    Time Frame
    Number of days of hospitalization from inclusion at M24
    Title
    RBC and WBC adherence
    Description
    Study of RBC and WBC adherence on lymphocytes subpopulation (including NK-T cells). Modulation of WBC and RBC surface markers by allograft.
    Time Frame
    at inclusion
    Title
    RBC and WBC adherence
    Description
    Study of RBC and WBC adherence on lymphocytes subpopulation (including NK-T cells). Modulation of WBC and RBC surface markers by allograft.
    Time Frame
    at 12 months
    Title
    RBC and WBC adherence
    Description
    Study of RBC and WBC adherence on lymphocytes subpopulation (including NK-T cells). Modulation of WBC and RBC surface markers by allograft.
    Time Frame
    at 24 months
    Title
    Expression of RBC and WBC surface markers
    Description
    Expression of RBC and WBC surface markers on lymphocytes subpopulation
    Time Frame
    at inclusion
    Title
    Expression of RBC and WBC surface markers
    Description
    Expression of RBC and WBC surface markers on lymphocytes subpopulation
    Time Frame
    at 12 months
    Title
    Expression of RBC and WBC surface markers
    Description
    Expression of RBC and WBC surface markers on lymphocytes subpopulation
    Time Frame
    at 24 months
    Title
    Mast cell mediator release
    Description
    Master cell mediator release will be assessed using plasma sample. Modulation of mast cell mediators release by allograft (tryptase, substance P and histamine)
    Time Frame
    at inclusion
    Title
    Mast cell mediator release
    Description
    Master cell mediator release will be assessed using plasma sample. Modulation of mast cell mediators release by allograft (tryptase, substance P and histamine)
    Time Frame
    at 12 months
    Title
    Mast cell mediator release
    Description
    Master cell mediator release will be assessed using plasma sample. Modulation of mast cell mediators release by allograft (tryptase, substance P and histamine)
    Time Frame
    at 24 months
    Title
    Inflammatory cytokines
    Description
    Inflammatory cytokines will be measured using serum sample. Modulation of inflammatory cytokine (TNF-alpha, IL-1, IL-6...) by allograft
    Time Frame
    at inclusion
    Title
    Inflammatory cytokines
    Description
    Inflammatory cytokines will be measured using serum sample. Modulation of inflammatory cytokine (TNF-alpha, IL-1, IL-6...) by allograft
    Time Frame
    at 12 months
    Title
    Inflammatory cytokines
    Description
    Inflammatory cytokines will be measured using serum sample. Modulation of inflammatory cytokine (TNF-alpha, IL-1, IL-6...) by allograft
    Time Frame
    at 24 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    15 Years
    Maximum Age & Unit of Time
    45 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Nathalie Dhedin
    Phone
    +33142385127
    Email
    nathalie.dhedin@aphp.fr
    First Name & Middle Initial & Last Name or Official Title & Degree
    Sylvie Chevret
    Phone
    +33142499742
    Email
    sylvie.chevret@paris7.jussieu.fr

    12. IPD Sharing Statement

    Learn more about this trial

    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

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