Immediate Allogeneic Hematopoietic Stem Cell Transplantation Versus Re-treatment for Patients With High-Risk Acute Myeloid Leukemia: a Randomised, Open-label, Phase 2 Clinical Trial.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 358
- 试验地点
- 4
- 主要终点
- treatment success
研究概览
简要总结
This study aims to investigate whether immediate HSCT for patients with high-risk AML and intermediate-risk AML who have not achieved complete remission (CR) after their first induction therapy is non-inferior to re-treatment with chemotherapy.
详细描述
- Disease control group: patients proceeded to allogeneic HSCT as soon as possible. Patients were allowed to receive low-dose chemotherapy that is not intended for the purpose of achieving a second remission.
- Retreatment group: Receive a second course of anti-leukemic treatment prior to allogeneic HSCT. The anti-leukemic treatment regimen will be determined based on the genetic mutation status. Patients without targetable mutations will receive a combination of BCL-2 inhibitors and demethylating agents as salvage chemotherapy. Patients with targetable mutations will receive appropriate targeted therapy (e.g., FLT3 inhibitors, IDH inhibitors).
For patients who have already received targeted therapy during induction treatment, the researchers may choose the treatment regimen based on the individual patient's condition.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •AML patients aged ≥ 18 years.
- •High-risk AML patients according to the 2022 ELN standards who received one cycle of induction therapy.
- •Requires allogeneic hematopoietic stem cell transplantation (including HLA-matched or mismatched allogeneic HSCT and unrelated donor transplant).
- •KPS score greater than
- •Informed consent must be signed before the start of the study procedures; if it is detrimental to the patient's condition for them to sign, the consent may be signed by a legal guardian or immediate family member.
排除标准
- •Acute promyelocytic leukemia.
- •Patient has received more than 440 mg/m2 daunorubicin equivalents. The cumulative dose is calculated by summing up isotoxic daunorubicin-equivalents for daunorubicin, doxorubicin, epirubicin, idarubicin and mitoxantrone. The conversion factors are derived from the comparison of the respective maximum doses. The conversion factor is 1 for daunorubicin, 1 for doxorubicin, 0.6 for epirubicin, 4.6 for idarubicin, and 2.7 for mitoxantrone (see worksheet for calculation).
- •Severe organ dysfunction, defined as:
- •Left ventricular ejection fraction <50%. 2) Patients who receive supplementary continuous oxygen. 3) Serum bilirubin >1.5 x ULN (if not considered Gilbert-Syndrome) or ASAT/ALAT >5 x ULN.
- •Estimated Glomerular Filtration Rate (GFR) < 50 ml/min, where: Estimated GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x (age in years)-0.203 x (0.742 if patient is female) x (1.212 if patient is black)
- •History of allogeneic transplantation.
- •Manifestation of AML in the Central Nervous System.
- •Pregnant or breastfeeding women.
研究组 & 干预措施
Disease control group
patients proceeded to allogeneic HSCT as soon as possible. Patients were allowed to receive low-dose chemotherapy that is not intended for the purpose of achieving a second remission.
干预措施: ImmediateAllogeneic Hematopoietic Stem Cell Transplantation (Other)
Retreatment group
Receive a second course of anti-leukemic treatment prior to allogeneic HSCT. The anti-leukemic treatment regimen will be determined based on the genetic mutation status. Patients without targetable mutations will receive a combination of BCL-2 inhibitors and demethylating agents as salvage chemotherapy. Patients with targetable mutations will receive appropriate targeted therapy (e.g., FLT3 inhibitors, IDH inhibitors).
干预措施: Retreatment (Other)
结局指标
主要结局
treatment success
时间窗: day 56 after allogeneic HCT
The primary endpoint, treatment success defined as complete remission on day 56 after allogeneic HCT, was defined as dichotomous success rate.
次要结局
- Cumulative Incidences of Allogeneic HSCT(HSCT rates at 4,8,16, and 24 weeks)
- Incidence of Complete Remission from Randomisation(Date of first documented CR or CRi or CRchim Death before CR/CRi/CRchim not achieve a CR or CRi by six months)
- Overall survival after HCT(Death)
- Event-free survival after HCT(death before relapse, relapse (both, hematological or molecular), and failure to achieve a CR at final remission assessment)
- Leukemia-free survival from day 56 after alloHCT for patients who met the primary endpoint(day 56)
- Rate of MRD Negative from Day 56 after HSCT(day 56)
- 7. Overall Survival from Randomization: Measured from the start of randomization, with the primary event being death.(Death)