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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)

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ClinicalTrials.gov Identifier: NCT04046705
Recruitment Status : Not yet recruiting
First Posted : August 6, 2019
Last Update Posted : September 23, 2019
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Study Description
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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.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Procedure: Allogeneic matched related haematopoietic stem cell transplantation Other: Standard arm Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : October 15, 2019
Estimated Primary Completion Date : October 15, 2024
Estimated Study Completion Date : October 15, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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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
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


Outcome Measures
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Primary Outcome Measures :
  1. 2 year event-free survival [ Time Frame: 2 years post-inclusion ]

    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 :
  1. Overall survival [ Time Frame: 2 years post-inclusion ]
  2. Number of days requiring hospitalization [ Time Frame: 1 year ]
    Number of days requiring hospitalization at 1 year post-inclusion with exclusion of the 5 first months post-inclusion

  3. Number of days requiring hospitalization [ Time Frame: 2 years post-inclusion ]
    Number of days requiring hospitalization at 2 years post-inclusion with exclusion of the 5 first months post-inclusion

  4. Number of vaso-occlusive crisis (VOC) requiring hospitalization [ Time Frame: 1 year post-inclusion ]
  5. Number of vaso-occlusive crisis (VOC) requiring hospitalization [ Time Frame: 2 years post-inclusion ]
  6. Number of acute chest syndrome (ACS) requiring hospitalization [ Time Frame: 1 year post-inclusion ]
  7. Number of acute chest syndrome (ACS) requiring hospitalization [ Time Frame: 2 years post-inclusion ]
  8. Number of hospitalizations in intensive care unit [ Time Frame: 1 year post-inclusion ]
  9. Number of hospitalizations in intensive care unit [ Time Frame: 2 years post-inclusion ]
  10. Number of priapism [ Time Frame: 1 year post-inclusion ]
  11. Number of priapism [ Time Frame: 2 years post-inclusion ]
  12. Number of stroke episodes [ Time Frame: 1 year post-inclusion ]
  13. Number of stroke episodes [ Time Frame: 2 years post-inclusion ]
  14. LDH count [ Time Frame: every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm ]
    Changes in LDH

  15. Percentage of patients with an aminotransferase value higher than five times the normal value [ Time Frame: every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm ]
    Changes in aminotransferase

  16. Percentage of patients with a gamma-GT value higher than five times the normal value [ Time Frame: every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm ]
    Changes in gamma-GT

  17. Percentage of patients with an Alkaline phosphatase value higher than five times the normal value [ Time Frame: every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm ]
    Changes in alkaline phosphatase

  18. Percentage of patients with a bilirubin value higher than three times the normal value [ Time Frame: every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm ]
    Changes in bilirubin

  19. Percentage of patients with a prothrombin value less than 70% [ Time Frame: every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm ]
    Changes in TP

  20. Activated partial thromboplastin time higher than 1.5 times the normal value [ Time Frame: every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm ]
    Changes in TCK

  21. Rate of hemoglobin [ Time Frame: every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm ]
    Changes in hemoglobin level

  22. Hematocrit [ Time Frame: every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm ]
    Changes in hematocrit

  23. 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 ]
    Changes in mean corpuscular volume

  24. 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 ]
    Changes of percentage of hemoglobin variants

  25. Reticulocyte count [ Time Frame: every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm ]
    Changes in percentage of reticulocyte

  26. White blood cells count [ Time Frame: every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm ]
    Changes in white blood cells

  27. Platelets counts [ Time Frame: every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm ]
    Changes in platelet counts

  28. Microalbuminuria/creatininuria ratio [ Time Frame: at 3 months ]
  29. Microalbuminuria/creatininuria ratio [ Time Frame: at 6 months ]
  30. Microalbuminuria/creatininuria ratio [ Time Frame: at 12 months ]
  31. Microalbuminuria/creatininuria ratio [ Time Frame: at 24 months ]
  32. Ferritin level [ Time Frame: at 3 months ]
  33. Ferritin level [ Time Frame: at 6 months ]
  34. Ferritin level [ Time Frame: at 12 months ]
  35. Ferritin level [ Time Frame: at 24 months ]
  36. Transferrin saturation level [ Time Frame: at 3 months ]
  37. Percentage of transferrin saturation [ Time Frame: at 6 months ]
  38. Percentage of transferrin saturation [ Time Frame: at 12 months ]
  39. Percentage of transferrin saturation [ Time Frame: at 24 months ]
  40. LH count [ Time Frame: at 24 months ]
    Gonadic function will be measured using LH

  41. FSH count [ Time Frame: at 24 months ]
    Gonadic function will be measured using FSH

  42. Testosterone count [ Time Frame: at 24 months ]
    Gonadic function will be measured using testosterone level in men

  43. Spermogram [ Time Frame: at 24 months ]
    Gonadic function will be measured using spermogram in men

  44. Oestrogen count [ Time Frame: at 24 months ]
    Gonadic function will be measured using oestrogen level in women

  45. AMH count [ Time Frame: at 24 months ]
    Gonadic function will be measured using AMH level in women

  46. Incidence of amenorrhea [ Time Frame: at 24 months ]
    Gonadic function will be measured using incidence of amenorrhea in women

  47. Number of parity [ Time Frame: at 24 months ]
  48. Percentage of patients with a proliferative retinopathy [ Time Frame: at 12 months ]
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)

  49. Percentage of patients with a proliferative retinopathy [ Time Frame: at 24 months ]
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)

  50. Percentage of patients with a hemorrhagic retinopathy [ Time Frame: at 12 months ]
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)

  51. Percentage of patients with a hemorrhagic retinopathy [ Time Frame: at 24 months ]
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)

  52. Percentage of patients with retinal detachment [ Time Frame: at 12 months ]
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)

  53. Percentage of patients with retinal detachment [ Time Frame: at 24 months ]
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)

  54. Proportion of patients with keratitis [ Time Frame: at 12 months ]
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)

  55. Proportion of patients with keratitis [ Time Frame: at 24 months ]
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)

  56. Proportion of patients with uveitis [ Time Frame: at 12 months ]
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)

  57. Proportion of patients with uveitis [ Time Frame: at 24 months ]
    Changes in retinopathy status (appearance, disappearance, improvement, aggravation)

  58. Tricuspid regurgitant jet velocity [ Time Frame: at 12 months ]
    Heart function will be assessed by a transthoracic echocardiography and using tricuspid régurgitant jet velocity

  59. Tricuspid regurgitant jet velocity [ Time Frame: at 24 months ]
    Heart function will be assessed by a transthoracic echocardiography and using tricuspid régurgitant jet velocity

  60. Left atrial dimension [ Time Frame: at 12 months ]
    Heart function will be assessed by a transthoracic echocardiography using left atrial dimension indexed to body surface

  61. Left atrial dimension [ Time Frame: at 24 months ]
    Heart function will be assessed by a transthoracic echocardiography using left atrial dimension indexed to body surface

  62. Left ventricular dimension [ Time Frame: at 12 months ]
    Heart function will be assessed by a transthoracic echocardiography using left ventricular dimension indexed to body surface

  63. Left ventricular dimension [ Time Frame: at 24 months ]
    Heart function will be assessed by a transthoracic echocardiography using left ventricular dimension indexed to body surface

  64. Ventricular mass index value [ Time Frame: at 12 months ]
    Heart function will be assessed by a transthoracic echocardiography using ventricular mass index

  65. Ventricular mass index value [ Time Frame: at 24 months ]
    Heart function will be assessed by a transthoracic echocardiography using ventricular mass index

  66. Left ventricular ejection fraction [ Time Frame: at 12 months ]
    Heart function will be assessed by a transthoracic echocardiography using left ventricular ejection fraction

  67. Left ventricular ejection fraction [ Time Frame: at 24 months ]
    Heart function will be assessed by a transthoracic echocardiography using left ventricular ejection fraction

  68. Forced Expiratory Volume in one second (FEV) [ Time Frame: at 12 months ]
    Lung function will be evaluated Forced Expiratory Volume in one second (FEV) , %

  69. Forced Expiratory Volume in one second (FEV) [ Time Frame: at 24 months ]
    Lung function will be evaluated Forced Expiratory Volume in one second (FEV) , %

  70. DLCO [ Time Frame: at 12 months ]
    Lung function will be evaluated using DLCO the diffusion capacity of carbon monoxide

  71. DLCO [ Time Frame: at 24 months ]
    Lung function will be evaluated using DLCO the diffusion capacity of carbon monoxide

  72. Forced vital capacity [ Time Frame: at 12 months ]
    Lung function will be evaluated using forced vital capacity (FVC)

  73. Forced vital capacity [ Time Frame: at 24 months ]
    Lung function will be evaluated using forced vital capacity (FVC)

  74. 6 minutes walk test [ Time Frame: at 12 months ]
    Lung function will be evaluated using 6 minutes walk test

  75. 6 minutes walk test [ Time Frame: at 24 months ]
    Lung function will be evaluated using 6 minutes walk test

  76. Number of new episodes of avascular osteonecrosis [ Time Frame: at 24 months ]
  77. Number of patients for each location of new episodes of avascular osteonecrosis [ Time Frame: at 24 months ]
    Location of new episodes of avascular osteonecrosis will be assessed using radiography and magnetic resonance imaging

  78. Fractures [ Time Frame: at 24 months ]
    Number of new episodes of fractures

  79. Central nervous system function [ Time Frame: at 12 months ]
    Central nervous system function will be assessed using magnetic resonance Imaging with ARM/MRI

  80. Central nervous system function [ Time Frame: at 24 months ]
    Central nervous system function will be assessed using magnetic resonance Imaging with ARM/MRI

  81. Iron overload [ Time Frame: at inclusion ]
    Iron overload will be assessed using liver and heart magnetic resonance Imaging in patients with ferritin > 1000 microg/L

  82. Iron overload [ Time Frame: at 12 months ]
    Iron overload will be assessed using liver and heart magnetic resonance Imaging in patients with ferritin > 1000 microg/L

  83. Iron overload [ Time Frame: at 24 months ]
    Iron overload will be assessed using liver and heart magnetic resonance Imaging in patients with ferritin > 1000 microg/L

  84. Red blood cell packed transfused [ Time Frame: at 24 months ]
    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)

  85. Number of delayed hemolytic transfusion reaction (DHTR) [ Time Frame: at 3 months ]
    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

  86. Number of delayed hemolytic transfusion reaction (DHTR) [ Time Frame: at 6 months ]
    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

  87. Number of delayed hemolytic transfusion reaction (DHTR) [ Time Frame: at 12 months ]
    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

  88. Number of delayed hemolytic transfusion reaction (DHTR) [ Time Frame: at 24 months ]
    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

  89. Proportion of patients with new RBC alloantibodies [ Time Frame: at 3 months ]
    New RBC alloantibodies will be assessed using blood test

  90. Proportion of patients with new RBC alloantibodies [ Time Frame: at 6 months ]
    New RBC alloantibodies will be assessed using blood test

  91. Proportion of patients with new RBC alloantibodies [ Time Frame: at 12 months ]
    New RBC alloantibodies will be assessed using blood test

  92. Proportion of patients with new RBC alloantibodies [ Time Frame: at 24 months ]
    New RBC alloantibodies will be assessed using blood test

  93. Percentage of patients with an oral opioid consumption [ Time Frame: at 3 months ]
  94. Percentage of patients with an oral opioid consumption [ Time Frame: at 6 months ]
  95. Percentage of patients with an oral opioid consumption [ Time Frame: at 12 months ]
  96. Percentage of patients with an oral opioid consumption [ Time Frame: at 24 months ]
  97. Quality of life evaluated using MOS SF36 questionnaire [ Time Frame: at 3 months ]
    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

  98. Quality of life evaluated using MOS SF36 questionnaire [ Time Frame: at 6 months ]
    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

  99. Quality of life evaluated using MOS SF36 questionnaire [ Time Frame: at 12 months ]
    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

  100. Quality of life evaluated using MOS SF36 questionnaire [ Time Frame: at 24 months ]
    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

  101. Depression and Anxiety status [ Time Frame: at 3 months ]

    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).


  102. Depression and Anxiety status [ Time Frame: at 6 months ]
    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).

  103. Depression and Anxiety status [ Time Frame: at 12 months ]

    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).


  104. Weight [ Time Frame: at 3 months ]
    Evolution of weight

  105. Weight [ Time Frame: at 6 months ]
    Evolution of weight

  106. Weight [ Time Frame: at 12 months ]
    Evolution of weight

  107. Weight [ Time Frame: at 24 months ]
    Evolution of weight

  108. Number of severe infections [ Time Frame: at 24 months ]
    A severe infection will be defined as a CTAE score of grade 3 or 4

  109. GvHD incidence [ Time Frame: at 12 months ]
  110. GvHD incidence [ Time Frame: at 24 months ]
  111. Grading of GvHD [ Time Frame: at 12 months ]
    Grading of GvHD will be assessed using magic consortium 2016 and NIH classification

  112. Chimerism in HSCT [ Time Frame: at 1 month ]
    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

  113. Chimerism in HSCT [ Time Frame: at 2 months ]
    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

  114. Chimerism in HSCT [ Time Frame: at 3 months ]
    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

  115. Chimerism in HSCT [ Time Frame: at 6 months ]
    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.

  116. Chimerism in HSCT [ Time Frame: at 9 months ]
    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

  117. Chimerism in HSCT [ Time Frame: at 12 months ]
    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

  118. Chimerism in HSCT [ Time Frame: at 18 months ]
    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

  119. Chimerism in HSCT [ Time Frame: at 24 months ]
    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

  120. Number of days of hospitalization [ Time Frame: Number of days of hospitalization from inclusion at M24 ]
    Number of days of hospitalization from inclusion

  121. RBC and WBC adherence [ Time Frame: at inclusion ]
    Study of RBC and WBC adherence on lymphocytes subpopulation (including NK-T cells). Modulation of WBC and RBC surface markers by allograft.

  122. RBC and WBC adherence [ Time Frame: at 12 months ]
    Study of RBC and WBC adherence on lymphocytes subpopulation (including NK-T cells). Modulation of WBC and RBC surface markers by allograft.

  123. RBC and WBC adherence [ Time Frame: at 24 months ]
    Study of RBC and WBC adherence on lymphocytes subpopulation (including NK-T cells). Modulation of WBC and RBC surface markers by allograft.

  124. Expression of RBC and WBC surface markers [ Time Frame: at inclusion ]
    Expression of RBC and WBC surface markers on lymphocytes subpopulation

  125. Expression of RBC and WBC surface markers [ Time Frame: at 12 months ]
    Expression of RBC and WBC surface markers on lymphocytes subpopulation

  126. Expression of RBC and WBC surface markers [ Time Frame: at 24 months ]
    Expression of RBC and WBC surface markers on lymphocytes subpopulation

  127. Mast cell mediator release [ Time Frame: at inclusion ]
    Master cell mediator release will be assessed using plasma sample. Modulation of mast cell mediators release by allograft (tryptase, substance P and histamine)

  128. Mast cell mediator release [ Time Frame: at 12 months ]
    Master cell mediator release will be assessed using plasma sample. Modulation of mast cell mediators release by allograft (tryptase, substance P and histamine)

  129. Mast cell mediator release [ Time Frame: at 24 months ]
    Master cell mediator release will be assessed using plasma sample. Modulation of mast cell mediators release by allograft (tryptase, substance P and histamine)

  130. Inflammatory cytokines [ Time Frame: at inclusion ]
    Inflammatory cytokines will be measured using serum sample. Modulation of inflammatory cytokine (TNF-alpha, IL-1, IL-6...) by allograft

  131. Inflammatory cytokines [ Time Frame: at 12 months ]
    Inflammatory cytokines will be measured using serum sample. Modulation of inflammatory cytokine (TNF-alpha, IL-1, IL-6...) by allograft

  132. Inflammatory cytokines [ Time Frame: at 24 months ]
    Inflammatory cytokines will be measured using serum sample. Modulation of inflammatory cytokine (TNF-alpha, IL-1, IL-6...) by allograft


Eligibility Criteria
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04046705


Contacts
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Contact: Nathalie Dhedin +33142385127 nathalie.dhedin@aphp.fr
Contact: Sylvie Chevret +33142499742 sylvie.chevret@paris7.jussieu.fr

Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
More Information
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT04046705    
Other Study ID Numbers: K170912J
First Posted: August 6, 2019    Key Record Dates
Last Update Posted: September 23, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
 Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn