Tyrosine Kinase Inhibitor Therapy Based on Molecular Monitoring of BCR/ABL Transcript Levels in Allogeneic Hematopoietic Stem Cell Transplant Recipients With Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 2 期
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Overall survival(OS)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of tyrosine kinase inhibitor(TKI) therapy based on molecular monitoring of BCR/ABL levels in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT).
详细描述
Philadelphia chromosome (Ph) is a reciprocal chromosomal translocation t(9;22）(q34;q11), which leads to the formation of the BCR/ABL oncogene. Ph is the most frequent cytogenetic abnormality in ALL characterized by poor outcome. With the BCR/ABL protein TKI, imatinib, in the combination chemotherapy regimes for newly diagnosed Ph+ ALL, more than 95% of patients can achieve complete remission(CR). Several studies have shown decreased relapse rates and improved disease-free survival for patients with imatinib-based treatment prior to allo-HSCT. However, the efficacy of maintenance therapy with imatinib after transplant for Ph+ ALL patients is still uncertain. In addition, acquired resistance to imatinib is frequently caused by point mutations in BCR/ABL that inactivate imatinib.
Detection of minimal residual disease (MRD) after transplant is associated with an increased risk of relapse. Reverse transcription-polymerase chain reaction (RT-PCR) is a sensitive method for detecting low-level BCR/ABL transcripts to assess MRD in Ph+ ALL. It has been corroborated by several reports that detection of MRD after SCT was predictive of imminent relapse.
In this study, we will evaluate the safety and efficacy of TKI therapy, when initiating treatment based on BCR-ABL transcript levels after allo-HSCT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •A patient age of 14-65 years
- •Allo-HSCT recipient with ph+ ALL
- •Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
排除标准
- •Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure)
- •patients with hematological relapse, extramedullary involvement of leukemia
- •Patients with any conditions not suitable for the trial (investigators' decision)
研究组 & 干预措施
TKI therapy
Treatment with TKI will be initiated if the level of BCR-ABL transcript in the bone marrow is detectable and transcript levels increased for two consecutive tests. TKIs will be given for patients without BCR/ABL mutations and sensitive TKIs will be given for those with mutations.
干预措施: TKIs (Drug)
结局指标
主要结局
Overall survival(OS)
时间窗: 2 years
OS is defined as continuous survival until death from any cause after HSCT.
次要结局
- Relapse rate(2 years)
- Disease-free survival(DFS)(2 years)
- Safety of TKI therapy(2 years)
研究者
Qifa Liu
Professor
Nanfang Hospital, Southern Medical University