Measurable Residual Disease Response-adapted Allogeneic Hematopoietic Stem Cell Transplantation for Adverse-risk Acute Myeloid Leukemia: an Open-label, Randomized, Controlled Trial（TROPHY-AML01）
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 178
- 试验地点
- 1
- 主要终点
- Event-free survival (EFS)
研究概览
简要总结
This TROPHY-AML01 regimen aims to identify the effectiveness and safety of MRD response-adapted allo-HSCT for adverse-risk acute myeloid leukemia in an open-label, randomized, controlled trial.
详细描述
1.1 Relapse is the most important cause of transplant failure Acute myeloid leukemia is one the most important hematologic malignancies for adults. According to the criteria of European LeukemiaNet (ELN) 2022, approximately 40%-50% of AML patients were categorized into adverse-risk group. The clinical outcomes of these patients receiving chemotherapy alone is poor and the 4-year probability of leukemia-free survival (LFS) after therapy is nearly 10%. Thus, allogeneic hematologic stem cell transplantation (allo-HSCT) is considered as the critical consolidation in adverse-risk AML patients, and many AML patients could achieve long-term LFS after allo-HSCT. However, nearly one third of the adverse-risk AML patients would experience relapse after allo-HSCT, and the outcomes of patients with post-transplant are very poor and relapse is also the most important cause of mortality after allo-HSCT. Thus, how to prevent post-transplant relapse is important to further improve the survival of patients with adverse-risk AML.
1.2 Measurable residual disease (MRD) can predict the relapse of AML after treatment.
The detection of MRD is one of the most important methods for defining the depth of remission. Using current sensitive techniques, the presence of 1 residual leukemia cell in 10 000-1 000 000 cells can be detected in patients with morphological complete remission (CR). The most commonly used method for MRD assessment involves (1) the determination of leukemia-associated immunophenotypic patterns (LAIPs) using multiparameter flow cytometry (MFC) and (2) the quantitative polymerase chain reaction (qPCR)-based evaluation of expression levels of leukemia-related genes, such as recurrent genetic abnormalities and other mutation types.
1.3 Pre-transplant MRD can predict the relapse of AML after allo-HSCT. MFC is one of the most common methods for MRD monitoring and is the most important method for MRD monitoring for those without leukemia-specific molecular markers. In the systemic review of Buckley et al., pre-transplant MRD was associated with worse LFS (hazard ratio [HR] = 2.76 [1.90-4.00]), overall survival (OS, HR = 2.36 [1.73-3.22]), and cumulative incidence of relapse (HR = 3.65 [2.53-5.27]).
1.4 The prognostic value of pre-transplant MRD positivity is controversial in adverse-risk AML.
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
- 16 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed AML;
- •Categorized into adverse-risk group according to ELN 2022 criteria;
- •16-65 years of age at the time of diagnosis;
- •achieving CR after 1 or 2 courses of induction chemotherapies;
- •ECOG PS score of 0 to 1 5) It needs consent from the patients or/and legal guardian, and signature on the Informed Consent.
排除标准
- •Newly diagnosed AML, but categorized into favorite- or intermediate-risk group according to ELN 2022 criteria;
- •< 16 years, or older than 65 years at the time of diagnosis;
- •Achieving CR after 3 or more courses of induction chemotherapies, or could not achieve CR after induction chemotherapies;
- •ECOG PS score of 2 or more;
- •Patients with other comorbidities or mental diseases that influence the life safety and compliance of patients as well as affect informed consent, enrollment in the research, follow-up visit or result interpretation.
结局指标
主要结局
Event-free survival (EFS)
时间窗: 1 year
EFS, defined as the time from the date of randomization to the date of MRD positivity, relapse, or death due to any cause.
次要结局
- Relapse(1 year)
- Acute graft-versus-host disease (aGvHD)(1 year)
- Chronic graft-versus-host disease (cGvHD)(1 year)
- Overall survival (OS)(1 year)
- Leukemia-free survival (LFS)(1 year)
- Non-relapse mortality (NRM)(1 year)
研究者
Xiao-Jun Huang
Director
Peking University People's Hospital