A Prospective Multicenter Clinical Trial of Treatment Strategy Based on MRD Level After 2 Initial Courses of Chemotherapy in Children and Young Adults With Acute Myeloid Leukemia
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 500
- 试验地点
- 4
- 主要终点
- relapse-free survival (RFS)
研究概览
简要总结
Minimal-residual disease (MRD) will be measured either by flow cytometry, or polymerase chain reaction (PCR) methods, in 3 check-points and it will be one of the decision-making control parameter for the optimal therapy tactics.
Patients with initially high-risk group and those with high MRD after 2 initial courses of chemotherapy will be assigned to the allogenic transplantation of the hematopoietic stem cells from Human Leucocyte Antigen (HLA) matched or haploidentical family donors.
详细描述
Genetic alterations in acute myeloid leukemia (AML) clone are well known prognostic risk factors of AML relapse. Standard risk group includes favorable t (15;17) (q22; q21) and inv (16)/t (16;16). High-risk patients have a complex karyotype rearrangement (3 and more), inversion of the long arm in 3rd chromosome and EVI1 gene rearrangement, monosomy 5 and 7, translocations involving KMT2A gene and several rare translocations. All other genotype alterations attributed to the moderate risk group.
Besides genetic factors, detection of the minimal residual disease (MRD) after initial chemotherapy and its decrease rate after 1st postremission chemotherapy with high dose Cytarabine and anthracyclines, plays a crucial role in the development of the morphologic relapse. Patients with PCR-MRD<0,1% after 2 courses of chemotherapy have a 30% or less risk of relapse, while PCR-MRD>0,1% - over 70%. In the clinical trial investigators are planning to measure MRD either by immune-phenotype, or PCR methods, in 3 check-points and it will be one of decision-making control parameter for the optimal therapy tactics.
Patients with initially high-risk group and those with high MRD after 2 initial courses of chemotherapy will be assigned to the allogenic transplantation of the hematopoietic stem cells from HLA- matched or haploidentical family donors.
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
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •de novo acute myeloid leukemia
- •signed informed consent
排除标准
- •diagnosis of: Fanconi anemia, acute promyelocytic leukemia, MDS, JMML, AML as secondary malignancy, Dawn syndrome.
结局指标
主要结局
relapse-free survival (RFS)
时间窗: 1 year
relapse-free survival from date of diagnosis till date of relapse, or date of death (whichever comes first) or date of last follow up
次要结局
- overall survival (OS)(1 year)
- event-free survival (EFS)(2 years)
- The proportion of of patients with severe adverse effects(6 months)
- The proportion of of patients with severe infections(1 month)
- The proportion of of patients with severe cardiotoxicity(1 year)
- MRD dynamic(1 months)
- MRD specificity and sensitivity(1, 2, 3 months)
- Cumulative incidence of relapse(6 months, 1 year)
- Cumulative incidence of transplant-related mortality(6 months after HSCT)
- Cumulative incidence of aGvHD II-IV grade(100 days after HSCT)
- Cumulative incidence of cGvHD(1 year after HSCT)