A Randomized, Multi-Center Phase III Trial Comparing Two Conditioning Regimens (CloFluBu and BuCyMel) in Children With Acute Myeloid Leukemia Undergoing Allogeneic Stem Cell Transplantation.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 170
- 试验地点
- 17
- 主要终点
- 2-year, acute grade III to IV-free, chronic non-limited GvH-free, relapse-free survival (GREF)
研究概览
简要总结
It is a randomized phase 3 study comparing two conditioning regimens in children with Acute Myeloid Leukemia, AML, undergoing allogenic stem cell transplantation. The primary aim is to investigate if a conditioning regimen containing one alkylator (Bu) combined with two antimetabolites (Clo and Flu) results in superior 2-year acute grade III to IV-free, chronic non-limited GvHD-free, relapse free survival than a conditioning regimen combining three alkylating agents (BuCyMel)
详细描述
The study is designed as an open-label randomized phase III, multicenter superiority trial comparing two conditioning regimens CloFluBu and BuCyMel in children with acute myeloid leukemia (AML) with per-protocol indications to allogeneic hematopoietic stem cell transplantation with a myeloablative conditioning.
This study is composed of two parts - an interventional part that includes randomization, and an observational part. The interventional part is a phase III randomized, open label, multicenter parallel group trial comparing two conditioning regimens used in pediatric HCT: a three alkylator combination of busulfan, cyclophosphamide and melphalan (BuCyMel, standard arm) and a combination of clofarabine, fludarabine and busulfan in which two alkylators are replaced by antimetabolites (CloFluBu, experimental arm). The observational part will prospectively register outcome measures of transplantation in patients not fulfilling criteria for participation in the interventional part of the study (due to lack of complete remission, lack of matched sibling or unrelated donor, who were not recruited to a national upfront protocol or who decline participation in randomization) but consenting to registration of the data.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
BuCyMel
a combination of busulfan, cyclophosphamide and melphalan, conditioning regimen
干预措施: busulfan, cyclophosphamide and melphalan, BuCyMel (Drug)
CloFluBu
a combination of clofarabine, fludarabine and busulfan conditioning regimen
干预措施: clofarabine, fludarabine and busulfan, CloFluBu (Drug)
结局指标
主要结局
2-year, acute grade III to IV-free, chronic non-limited GvH-free, relapse-free survival (GREF)
时间窗: 2 years
To investigate if a conditioning regimen containing one alkylator (Bu) combined with two antimetabolites (Clo and Flu) results in superior 2-year acute grade III to IV-free, chronic non-limited GvHD-free, relapse free survival (GRFS) than a conditioning regimen combining three alkylating agents (BuCyMel)
次要结局
- Incidence of chronic GVHD(2 years)
- Incidence of grade II-IV and III-IV acute GVHD(+180 days post transplantation)
- Overall survival(2 years)
- Immunological recovery(2 years)
- Neutrophil and platelet engraftment(28 days post transplantation)
- Primary graft failure(+28 days post transplantation)
- Secondary graft failure(2 years)
- The association between pre-HCT MRD and relapse(2 years)
- Cumulative incidence of transplant-related mortality(2 years)
- Disease-free survival(2 years)
- Incidence of grade ≥ 3 toxicity Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease(+ 100 days post transplantation)
- Incidence of grade ≥ 3 toxicity Engraftment Syndrome (ES)(2 years)
- Incidence of grade ≥ 3 toxicity Transplant-associated thrombotic microangiopathy (TA-TMA)(2 years)
- Incidence of grade ≥ 3 toxicity Hemorrhagic Cystitis (HC)(2 years)
- Incidence of grade ≥ 3 infections(2 years)
- Health-Related Quality of Life, HRQoL.(2 years)
- Transplant-associated hormonal and gonadal late effects(2 years)
- Nutritional status(2 years)
- Cumulative incidence of relapse(2 years)