A Randomized Controlled Study of Tyrosine Kinase Inhibitor Maintenance Therapy Following Allogeneic Hematopoietic Stem Cell Transplantation in Newly Diagnosed Philadelphia Chromesome Positive Adult Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 不适用
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Percentage of Patients with Complete Remission (CR)
研究概览
简要总结
This project is a key clinical research project approved by the Clinical Research Center of the First Affiliated Hospital of Xi 'an Jiaotong University.Tyrosine kinase inhibitors (TKI) combined with chemotherapy and subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT) are routinely used in patients with philadelpha-positive lymphoblastic leukemia (Ph+ALL). However, TKI maintenance therapy post-HSCT remains controversial. In this study, Ph+ALL patients are enrolled and given dasatinib combined with chemotherapy followed by allo-HSCT. Then patients in the group A continuing to use dasatinib for 1 year is compared with those in the group B receiving dasatinib for 6 months after HSCT. The measurable residual disease (MRD), complete remission (CR), overall survival (OS), disease free survival (DFS), non-relapse mortality (NRM) and the incidence of graft versus host disease (GVHD) will be observed to determine the optimal duration of TKI maintenance therapy post-HSCT.
详细描述
About 25% of adult patients with acute lymphoblastic leukemia (ALL) are associated with t (9; 22), positive philadelphia chromosome (Ph+ ALL), in whom BCR/ABL fusion gene can be detected in the bone marrow and peripheral blood. Although current treatment strategies using tyrosine kinase inhibitors (TKIs) such as dasatinib combined with chemotherapy have achieved high complete remission (CR) rates, the duration of remission is short, and most Ph+ ALL patients relapse within 2 years. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) bridging to CR remains the only strategy to cure Ph+ ALL. However, TKI maintenance therapy post-HSCT remains controversial. In this study, Ph+ALL patients are enrolled. The participants will receive dasatinib combined with induction and consolidation chemotherapy to obtain molecular remission and then undergo allo-HSCT. After the above treatments, the patients will be randomly divided into two groups. The subjects in the group A will continue to use dasatinib for 1 year, while the patients in the group B receive dasatinib for 6 months post-HSCT. The measurable residual disease (MRD), CR, overall survival (OS), disease free survival (DFS), non-relapse mortality (NRM) and the incidence of graft versus host disease (GVHD) will be observed to determine the optimal duration of TKI maintenance therapy post-HSCT.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18-65 years old, newly diagnosed as Ph+ALL.
- •Sign the informed consent.
- •Have appropriate allo-HSCT donors.
- •Accept allo-HSCT.
- •Accept follow-up.
排除标准
- •Liver and kidney function impairment: serum transaminase > 2 times of the upper limit of normal value, total bilirubin > 1.5 times of the upper limit of normal value, serum inosine > the upper limit of normal value (97 umol/L).
- •Active hepatitis B, hepatitis C or tuberculosis infection.
- •Can not tolerate the adverse effects of dasatinib.
- •Pregnancy.
- •Diagnosis of mental disorders.
- •Failed to reach molecular complete remission (MCR) after the early treatment.
- •Do not accept follow-up.
研究组 & 干预措施
Dasatinib for 1 year
After the allo-HSCT treatment, the patients in this group will continue to take dasatinib orally for 1 year.
干预措施: Dasatinib (Drug)
Dasatinib for 6 months
After the allo-HSCT treatment, the patients in this group will receive dasatinib for 6 months.
干预措施: Dasatinib (Drug)
结局指标
主要结局
Percentage of Patients with Complete Remission (CR)
时间窗: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
CR means that the blood counts have returned to normal, the leukemia cannot be seen when a bone marrow sample is examined under the microscope, and the signs and symptoms of the ALL are gone.
Percentage of Patients with Measurable Residual Disease (MRD) Positivity
时间窗: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
MRD means the subclinical levels of residual leukemia.
次要结局
- Overall Survival (OS), months(From date of randomization until the date of death from any cause, whichever came first, assessed up to 36 months.)
- Non-relapse Mortality (NRM), rate or percentage(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.)
- Incidence of graft versus host disease (GVHD), rate or percentage(From date of randomization until the date of GVHD occurrence or date of death from any cause, whichever came first, assessed up to 36 months.)
- Adverse Effects (AE)(From date of randomization until the date of death from any cause, whichever came first, assessed up to 36 months.)
- Disease-free Survival (DFS), months(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.)