A Phase II Multicentre, Randomized, Controlled Open-label Study on the Use of Anti-thymocyte Globulin and Rituximab for Immunomodulation of Graft-versus-host Disease in Allogeneic Matched Transplants for Non Malignancies
试验速览
- 阶段
- 2 期
- 入组人数
- 130
- 试验地点
- 4
- 主要终点
- Acute graft-versus-host disease (aGVHD) II-IV and chronic GvHD
研究概览
简要总结
• The primary aim of the present trial is to assess in a randomized fashion the benefit on standard graft-versus-host disease (GVHD) prophylaxis of the addition of ATG-Fresenius S ® in transplants from matched related donors (MRD) and of anti-CD20 rituximab in transplants from matched unrelated donors (MUD). Both safety and efficacy of the treatment will be assessed, in particular in respect to the clinical status of the patient, i.e. prevention of graft failure and chronic GvHD and of Ebstein Barr virus (EBV) viremia for MUD patients.
The conditioning proposed combines myeloablative drugs with a favorable safety profile such as treosulfan, thiotepa (Tepadina®) and fludarabine with the intent to reduce the traditional immediate and late toxicity of busulfan and cyclophosphamide.
详细描述
For patients transplanted from a MRD
The primary end-point is the cumulative incidence of a combined end-point defined as the time from randomization to:
- primary and secondary graft failure,
- aGVHD II-IV,
- cGVHD,
- death, whichever occurs first.
For patients transplanted from a MUD
The primary end-point is the cumulative incidence of a combined end-point defined as the time from randomization to:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 28 Days 至 64 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •non malignant haematological and inherited metabolic disorders benefiting from an allogeneic HSCT conditioned with a myeloablative regimen
- •Availability of a matched related donor (MRD) or Matched Unrelated Donor (MUD)
- •Lansky or Karnofsky Index ≥ 60
- •Inherited metabolic disorders: DQ ≥ 70 (+ MRI Loes score ≤ 9 for adrenoleukodystrophy)
- •Adequate cardiac, renal, hepatic and pulmonary functions as evidenced by:
- •Serum creatinine ≤ 1.5 × upper limit of normal (ULN)
- •Heart shortening fraction (left-ventricle) > 28 % or LVEF > 55%
- •Serum bilirubin ≤ 1.5 × ULN (except for Wolman disease),
- •AST and ALT ≤ 2.5 × ULN (except for thalassemic syndromes and Wolman disease)
- •Pulmonary function: if cooperative: FEV1 and FVC on pulmonary function testing > 60 %; if non cooperative: pulse oximetry > 95 % in room air
- •Availability of autologous back up marrow (> 2 x 108 TNC+ cells/kg or > 2 x 106 CD34+ cells/kg) for MUD
- •Adequate contraception in female patients of child-bearing potential
- •Signed informed consent
排除标准
- •Any malignancy
- •Liver cirrhosis evidenced on liver histology (performed in suspicious cases or in case of Wolman disease)
- •HIV- positivity
- •Clinically significant pleural effusion or ascites
- •Pregnancy or lactation
- •Known hypersensitivity to trial drugs
- •Participation in another experimental drug trial in the 2 months preceding enrollment
- •Non-cooperative behaviour or non-compliance
- •Previous HSCT
研究组 & 干预措施
MRD-Regimen&Polyclonal antibody
Patients MRD will be randomized to receive Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 & ATG-Fresenius S® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2
干预措施: polyclonal antibody (Biological)
MRD-Regimen&Polyclonal antibody
Patients MRD will be randomized to receive Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 & ATG-Fresenius S® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2
干预措施: Treosulfan (Drug)
MRD-Regimen&Polyclonal antibody
Patients MRD will be randomized to receive Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 & ATG-Fresenius S® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2
干预措施: Fludarabine (Drug)
MRD-Regimen&Polyclonal antibody
Patients MRD will be randomized to receive Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 & ATG-Fresenius S® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2
干预措施: Thiotepa (Drug)
MRD-Regimen&Polyclonal antibody
Patients MRD will be randomized to receive Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 & ATG-Fresenius S® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2
干预措施: Cyclosporine A (Drug)
MRD-Regimen&Polyclonal antibody
Patients MRD will be randomized to receive Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 & ATG-Fresenius S® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2
干预措施: Methotrexate (Drug)
MRD-Regimen
Patients receiving stem cell transplantation from a matched related donors (MRD) will be randomized to receive only Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 (total dose of 42 g/m²) + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 (total dose of 150 mg/m²) after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals (total dose of 8 mg/kg)+ Cyclosporine A iv at a starting dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL (In the absence of GvHD CSA will be tapered after day + 180 and stopped at 9-12 months) + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6
干预措施: Treosulfan (Drug)
MRD-Regimen
Patients receiving stem cell transplantation from a matched related donors (MRD) will be randomized to receive only Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 (total dose of 42 g/m²) + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 (total dose of 150 mg/m²) after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals (total dose of 8 mg/kg)+ Cyclosporine A iv at a starting dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL (In the absence of GvHD CSA will be tapered after day + 180 and stopped at 9-12 months) + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6
干预措施: Fludarabine (Drug)
MRD-Regimen
Patients receiving stem cell transplantation from a matched related donors (MRD) will be randomized to receive only Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 (total dose of 42 g/m²) + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 (total dose of 150 mg/m²) after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals (total dose of 8 mg/kg)+ Cyclosporine A iv at a starting dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL (In the absence of GvHD CSA will be tapered after day + 180 and stopped at 9-12 months) + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6
干预措施: Thiotepa (Drug)
MRD-Regimen
Patients receiving stem cell transplantation from a matched related donors (MRD) will be randomized to receive only Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 (total dose of 42 g/m²) + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 (total dose of 150 mg/m²) after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals (total dose of 8 mg/kg)+ Cyclosporine A iv at a starting dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL (In the absence of GvHD CSA will be tapered after day + 180 and stopped at 9-12 months) + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6
干预措施: Cyclosporine A (Drug)
MRD-Regimen
Patients receiving stem cell transplantation from a matched related donors (MRD) will be randomized to receive only Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 (total dose of 42 g/m²) + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 (total dose of 150 mg/m²) after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals (total dose of 8 mg/kg)+ Cyclosporine A iv at a starting dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL (In the absence of GvHD CSA will be tapered after day + 180 and stopped at 9-12 months) + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6
干预措施: Methotrexate (Drug)
MUD-Regimen & Rituximab
Patients MUD will be randomized to receive Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 and at a dose of 10 mg/m2 on day +11 + ATG-Fresenius S ® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2 & Rituximab in a single infusion of 200 mg/m2 on day -1
干预措施: polyclonal antibody (Biological)
MUD-Regimen & Rituximab
Patients MUD will be randomized to receive Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 and at a dose of 10 mg/m2 on day +11 + ATG-Fresenius S ® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2 & Rituximab in a single infusion of 200 mg/m2 on day -1
干预措施: Rituximab (Drug)
MUD-Regimen & Rituximab
Patients MUD will be randomized to receive Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 and at a dose of 10 mg/m2 on day +11 + ATG-Fresenius S ® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2 & Rituximab in a single infusion of 200 mg/m2 on day -1
干预措施: Treosulfan (Drug)
MUD-Regimen & Rituximab
Patients MUD will be randomized to receive Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 and at a dose of 10 mg/m2 on day +11 + ATG-Fresenius S ® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2 & Rituximab in a single infusion of 200 mg/m2 on day -1
干预措施: Fludarabine (Drug)
MUD-Regimen & Rituximab
Patients MUD will be randomized to receive Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 and at a dose of 10 mg/m2 on day +11 + ATG-Fresenius S ® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2 & Rituximab in a single infusion of 200 mg/m2 on day -1
干预措施: Thiotepa (Drug)
MUD-Regimen & Rituximab
Patients MUD will be randomized to receive Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 and at a dose of 10 mg/m2 on day +11 + ATG-Fresenius S ® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2 & Rituximab in a single infusion of 200 mg/m2 on day -1
干预措施: Cyclosporine A (Drug)
MUD-Regimen & Rituximab
Patients MUD will be randomized to receive Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 and at a dose of 10 mg/m2 on day +11 + ATG-Fresenius S ® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2 & Rituximab in a single infusion of 200 mg/m2 on day -1
干预措施: Methotrexate (Drug)
MUD-Regimen
Patients MUD will be randomized to receive only Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 and at a dose of 10 mg/m2 on day +11 + ATG-Fresenius S ® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2
干预措施: polyclonal antibody (Biological)
MUD-Regimen
Patients MUD will be randomized to receive only Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 and at a dose of 10 mg/m2 on day +11 + ATG-Fresenius S ® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2
干预措施: Treosulfan (Drug)
MUD-Regimen
Patients MUD will be randomized to receive only Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 and at a dose of 10 mg/m2 on day +11 + ATG-Fresenius S ® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2
干预措施: Fludarabine (Drug)
MUD-Regimen
Patients MUD will be randomized to receive only Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 and at a dose of 10 mg/m2 on day +11 + ATG-Fresenius S ® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2
干预措施: Thiotepa (Drug)
MUD-Regimen
Patients MUD will be randomized to receive only Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 and at a dose of 10 mg/m2 on day +11 + ATG-Fresenius S ® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2
干预措施: Cyclosporine A (Drug)
MUD-Regimen
Patients MUD will be randomized to receive only Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 and at a dose of 10 mg/m2 on day +11 + ATG-Fresenius S ® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2
干预措施: Methotrexate (Drug)
结局指标
主要结局
Acute graft-versus-host disease (aGVHD) II-IV and chronic GvHD
时间窗: From date of randomization assessed up to 100 months
For patients transplanted from a MRD The cumulative incidence of a combined end-point defined as the time from randomization to: * primary and secondary graft failure, * aGVHD II-IV, * cGVHD, * death, whichever occurs first. For patients transplanted from a MUD The cumulative incidence of a combined end-point defined as the time from randomization to: * aGVHD II-IV, * EBV viremia, whichever occurs first.
次要结局
- Chronic graft-versus-host disease (cGVHD)(From date of randomization assessed up to 100 months)
- Overall survival (OS)(From date of randomization assessed up to 100 months)
- Treatment related mortality (TRM)(From date of randomization assessed up to 100 months)
研究者
Franco Locatelli
Director Department of Pediatric Hematology and Oncology
Bambino Gesù Hospital and Research Institute