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
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 78
- 主要终点
- 2 year event-free survival
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 15 Years 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
HLA matched haematopoietic stem cell transplantation
Peripheral blood stem cell from matched HLA related donor.
干预措施: Allogeneic matched related haematopoietic stem cell transplantation (Procedure)
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.
干预措施: Standard arm (Other)
结局指标
主要结局
2 year event-free survival
时间窗: 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
次要结局
- Overall survival(2 years post-inclusion)
- Number of days requiring hospitalization(2 years post-inclusion)
- Number of vaso-occlusive crisis (VOC) requiring hospitalization(2 years post-inclusion)
- Number of acute chest syndrome (ACS) requiring hospitalization(2 years post-inclusion)
- Number of hospitalizations in intensive care unit(2 years post-inclusion)
- Number of priapism(2 years post-inclusion)
- Number of stroke episodes(2 years post-inclusion)
- LDH count(every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm)
- Percentage of patients with an aminotransferase value higher than five times the normal value(every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm)
- Percentage of patients with a gamma-GT value higher than five times the normal value(every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm)
- Percentage of patients with an Alkaline phosphatase value higher than five times the normal value(every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm)
- Percentage of patients with a bilirubin value higher than three times the normal value(every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm)
- Percentage of patients with a prothrombin value less than 70%(every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm)
- Activated partial thromboplastin time higher than 1.5 times the normal value(every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm)
- Rate of hemoglobin(every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm)
- Hematocrit(every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm)
- AMH count(at 24 months)
- Number of parity(at 24 months)
- Mean corpuscular volume(every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm)
- Hemoglobin variants(every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm)
- Reticulocyte count(every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm)
- White blood cells count(every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm)
- Platelets counts(every 3 months (from inclusion to 24 months) and at Month 1, Month 2 and Month 3 in the transplant arm)
- Microalbuminuria/creatininuria ratio(at 24 months)
- Ferritin level(at 24 months)
- Transferrin saturation level(at 3 months)
- Percentage of transferrin saturation(at 24 months)
- LH count(at 24 months)
- Oestrogen count(at 24 months)
- FSH count(at 24 months)
- Testosterone count(at 24 months)
- Spermogram(at 24 months)
- Incidence of amenorrhea(at 24 months)
- Percentage of patients with a proliferative retinopathy(at 24 months)
- Percentage of patients with a hemorrhagic retinopathy(at 24 months)
- Percentage of patients with retinal detachment(at 24 months)
- Proportion of patients with keratitis(at 24 months)
- Proportion of patients with uveitis(at 24 months)
- Tricuspid regurgitant jet velocity(at 24 months)
- Left atrial dimension(at 24 months)
- Left ventricular dimension(at 24 months)
- Ventricular mass index value(at 24 months)
- Left ventricular ejection fraction(at 24 months)
- Forced Expiratory Volume in one second (FEV)(at 24 months)
- DLCO(at 24 months)
- Forced vital capacity(at 24 months)
- 6 minutes walk test(at 24 months)
- Number of new episodes of avascular osteonecrosis(at 24 months)
- Number of patients for each location of new episodes of avascular osteonecrosis(at 24 months)
- Fractures(at 24 months)
- Central nervous system function(at 24 months)
- Iron overload(at 24 months)
- Red blood cell packed transfused(at 24 months)
- Number of delayed hemolytic transfusion reaction (DHTR)(at 24 months)
- Proportion of patients with new RBC alloantibodies(at 24 months)
- Percentage of patients with an oral opioid consumption(at 24 months)
- Quality of life evaluated using MOS SF36 questionnaire(at 24 months)
- Depression and Anxiety status(at 12 months)
- Weight(at 24 months)
- Number of severe infections(at 24 months)
- GvHD incidence(at 24 months)
- Grading of GvHD(at 12 months)
- Chimerism in HSCT(at 24 months)
- Number of days of hospitalization(Number of days of hospitalization from inclusion at M24)
- RBC and WBC adherence(at 24 months)
- Expression of RBC and WBC surface markers(at 24 months)
- Mast cell mediator release(at 24 months)
- Inflammatory cytokines(at 24 months)