Prospective Randomized Study of the Incidence and Outcome of Veno-Occlusive Disease (VOD) With the Prophylactic Use of Defibrotide (DF) in Pediatric Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 360
- 试验地点
- 23
- 主要终点
- The primary objective is to evaluate if prophylactic DF has an impact on the incidence of VOD
研究概览
简要总结
The aim of this trial is to evaluate whether the prophylactic use of Defibrotide (DF) in pediatric patients (age less than 18 years) undergoing stem cell transplantation and who are at high risk of developing hepatic Veno-occlusive Disease (VOD) will have an impact on the incidence and severity of the disease. Patients will be randomly assigned to one of two treatment arms: Those allocated to the Prophylactic Arm will receive the study drug (Defibrotide) from the day of conditioning onwards. Patients allocated to the Control Arm will receive the study drug (Defibrotide) from the day that VOD is diagnosed.
详细描述
Comparison/control intervention and duration of the intervention:
Patients will be assigned randomly to either the Defibrotide (DF) prophylaxis arm or the control arm. Those allocated to the DF prophylaxis arm (DF 25 mg/kg/d iv in 4 doses) will begin treatment at day of conditioning and stop at day +30 after Stem Cell Transplantation (SCT) or upon discharge from inpatient care. There is no dose adjustment for a patient of the study arm who developed VOD, they continue with the 25mg/kg/d iv.
Patients allocated to the control arm receive no prophylactic measures and will start DF (25 mg/kg/d iv in 4 doses) beginning at day of diagnosis of Veno-occlusive Disease (VOD) according to modified Seattle criteria. Treatment will be stopped at complete resolution of symptoms. In both arms patients who developed VOD will continue DF until:
- complete resolution of the ascites and
- reversion of the hepatopedal flow (if present) and
- normalization of the total and direct bilirubin
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
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age <18 years
- •myeloablative conditioning and autologous or allogeneic stem cell transplantation with at least one of the following risk factors for VOD:
- •Pre-existing liver disease
- •Second myeloablative HSCT
- •History of treatment with gemtuzumab ozogamicin (MYLOTARGÒ, GO, CMA-676, Wyeth)
- •Allogeneic HSCT for leukemia beyond the second relapse
- •Osteopetrosis (OP)
- •Conditioning with busulfan and melphalan
- •Macrophage activating syndromes (MAS, like hemophagocytic lymphohistiocytosis, Griscelli, Chediak-Higashi
- •Adrenoleukodystrophy (ALD)
排除标准
- •Pregnant patients
- •Patients who are transplanted but do not fulfill any of the above mentioned criteria
研究组 & 干预措施
Prophylaxis Arm
干预措施: Defibrotide (Drug)
Control Arm
干预措施: Defibrotide (Drug)
结局指标
主要结局
The primary objective is to evaluate if prophylactic DF has an impact on the incidence of VOD
时间窗: Day + 30 post HSCT
次要结局
- Occurrence of Multi-System Organ Failure and Survival (all causes of mortality)(day +100 post HSCT)