Effect of Prophylactic Tyrosine Kinase Inhibitor Therapy Post-transplants on Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia Undergoing Allo-HSCT With Minimal Residual Disease Positive Pre-transplants
试验速览
- 阶段
- 2 期
- 入组人数
- 82
- 试验地点
- 1
- 主要终点
- Overall survival(OS)
研究概览
简要总结
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in early first complete remission improves the long-term outcomes for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Relapse remains a major cause of treatment failure even after allo-HSCT. The prevention of relapse is essential for improving the outcome of Ph+ ALL. Our previous clinical trial (ID: NCT01883219) demonstrated that pre-emptive tyrosine kinase inhibitor (TKIs) administration based on minimal residual disease (MRD) and BCR-ABL mutation after allo-HSCT might reduce the incidence of relapses and improve survival for patients with Ph+ ALL. Moreover, our result suggested that Ph+ ALL with MRD positive pre-transplants had the higher rate of molecular biology relapse. In this study, we will evaluate the safety and efficacy of prophylactic TKI therapy post-transplants on Ph+ ALL undergoing allo-HSCT with MRD positive pre-transplants.
详细描述
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in early first complete remission improves the long-term outcomes for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Relapse remains a major cause of treatment failure even after allo-HSCT. Overall, patients experiencing relapse have a dismal prognosis despite salvage treatment with TKIs. The prevention of relapse is essential for improving the outcome of Ph+ ALL. Strategies to prevent relapse include tyrosine kinase inhibitor (TKIs) use, donor lymphocyte infusions (DLI), CAR-T and so on. At present, the utility of TKIs administration post-transplants is controversial. Our previous clinical trial (ID: NCT01883219) demonstrated that pre-emptive TKI administration based on minimal residual disease (MRD) and BCR-ABL mutation after allo-HSCT might reduce the incidence of relapses and improve survival for patients with Ph+ ALL. Moreover, we found that 58% Ph+ ALL with MRD positive pre-transplants would MRD positive post-transplants, whereas only 11.4% Ph+ ALL with MRD negative pre-transplants would MRD positive post-transplants, suggesting that Ph+ ALL with MRD positive pre-transplants had the higher rate of molecular biology relapse. In this study, we will evaluate the safety and efficacy of prophylactic TKI therapy post-transplants on Ph+ ALL undergoing allo-HSCT with MRD positive pre-transplants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 65 Years(Child, Adult, Older Adult)
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient age of 14-65 years
- •Ph+ ALL undergoing allo-HSCT with MRD positive pre-transplants
- •Survival > 30 days post-transplants
- •MRD negative on day +30 post-transplants
排除标准
- •Ph+ ALL undergoing allo-HSCT with MRD negative pre-transplants
- •Survival <30 days post-transplants
- •MRD positive on day +30 post-transplants
- •Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure)
- •Patients with any conditions not suitable for the trial (investigators' decision)
研究组 & 干预措施
Prophylactic TKI Therapy
Treatment with prophylactic TKI will be initiated from day +30 to +60 post-transplants. TKI was selected according to the mutation results of ABL kinase region.
干预措施: Tyrosine kinase inhibitor (TKIs) (Drug)
结局指标
主要结局
Overall survival(OS)
时间窗: 2 year
the time from the date of transplantation to death or the last day of follow-up
次要结局
- Relapse rate(2 year)
- Disease-free survival(DFS)(2 year)
- Adverse effects of TKI therapy(2 year)
研究者
Qifa Liu
Professor
Nanfang Hospital, Southern Medical University
