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SHR2554/AZA + Overlapped Modified BUCY for High-risk/Relapsed Leukemia/MDS

2026年6月8日 更新者:Limin Liu,MD、The First Affiliated Hospital of Soochow University

A Prospective, Multicenter, Open-label, Randomized Controlled Trial of SHR2554 Plus Azacitidine in Overlapped Sequential Combination With Modified BUCY Conditioning Regimen in Patients With High-risk or Relapsed/Refractory Acute Leukemia and Myelodysplastic Neoplasms Secondary IDs

This study was designed as a prospective, multicenter, open-label, randomized controlled trial. Eligible participants were patients aged 15-65 years with high risk or relapsed/refractory acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic neoplasms (MDS), diagnosed based on bone marrow morphology, immunophenotyping, genetic testing, and treatment response assessment. The experimental group received SHR2554 combined with azacitidine as an overlapped sequential combination with the mBuCy conditioning regimen, whereas the control group received the mBuCy conditioning regimen, both followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). The primary endpoint is 1-year event-free survival (EFS). Secondary endpoints include 2-year overall survival, 2-year cumulative incidence of relapse, transplant-related mortality, incidence of acute/chronic GVHD, and safety profiles.

研究概览

研究类型

介入性

注册 (估计的)

180

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习联系方式

学习地点

    • Jiangsu
      • Suzhou、Jiangsu、中国、215006
        • The First Affiliated Hospital of Soochow University

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 成人
  • 年长者

接受健康志愿者

不

描述

Inclusion Criteria:

  1. Age 15-60 years, of either sex.
  2. Diagnosis of AML or ALL according to the WHO 2022 criteria, with an indication for allogeneic hematopoietic stem cell transplantation:

    AML with high-risk genetics at diagnosis (risk stratification per ELN 2022) or relapsed/refractory AML (meeting any of the following: refractory-failure to achieve complete remission (CR) after two cycles of induction chemotherapy; relapse-reappearance of blasts in peripheral blood or bone marrow (≥5%) after first CR, or extramedullary relapse (EMR)).

    High-risk B-ALL at diagnosis (risk stratification per ELN 2022) or pre-transplant MRD-positive B-ALL.

    Confirmed T-ALL. History of central nervous system leukemia (CNSL) or pathologically confirmed extramedullary disease (EMD) during AML or ALL.

    Myelodysplastic neoplasms (MDS): IPSS score intermediate-2 or high; IPSS-R score high or very high; IPSS-M score high or very high.

  3. Availability of an appropriate HLA-matched donor.4: ECOG performance status 0-2.5: Adequate major organ function, defined as: Left ventricular ejection fraction ≥50%. Pulmonary function: DLCO ≥50% of predicted value. Liver function: ALT/AST ≤3×ULN, total bilirubin ≤2×ULN. Renal function: estimated creatinine clearance (CrCl) ≥60 mL/min.6: Ability to understand the study and voluntary signed informed consent.

Exclusion Criteria:

1: Acute promyelocytic leukemia (APL);2: Active central nervous system leukemia;3: Prior allogeneic hematopoietic stem cell transplantation;4: Prior treatment with any EZH2 inhibitor;5: Uncontrolled active infection as assessed by the investigator;6: Myocardial infarction or unstable angina within the previous 6 months;7: Known hypersensitivity to SHR2554, azacitidine, or any excipient of the mBuCy regimen;8: Pregnant or breastfeeding women;9: Any other medical condition that, in the investigator's judgment, would preclude study enrollment.

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:随机化
  • 介入模型:并行分配
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
实验性的:Experimental: SHR2554/AZA + Overlapped mBUCY
SHR2554 350 mg BID and azacitidine 75 mg/m² daily on days -9 to -3, overlapping with mBUCY conditioning:semustine 250 mg/m² on day -8; cytarabine 2 g/m² q12h on day -7; busulfan 0.8 mg/kg q6h on days -6,-5, -4 (total 3.2 mg/kg/day); cyclophosphamide 1.8 g/ m²/day on days -3 and -2.
有源比较器:Active Comparator: mBUCY conditioning Regimen Group
semustine 250 mg/m² on day -8; cytarabine 2 g/m² q12h on day -7; busulfan 0.8 mg/kg q6h on days -6,-5, -4 (total 3.2 mg/kg/day); cyclophosphamide 1.8 g/ m²/day on days -3 and -2

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
Event-Free Survival (EFS)
大体时间:1 years
It is measured from the time of entry into this trial to the date of first event (relapse, death from any cause); patients not known to have experienced any event at last follow-up are censored on the date they were last known to be event-free.
1 years

次要结果测量

结果测量
措施说明
大体时间
总生存期(OS)
大体时间:2年
从进入本试验之日起至因任何原因死亡之日计算;在最后一次随访中不知道已经死亡的患者在他们最后一次知道还活着的日期被审查。
2年
造血重建的时间段
大体时间:24周
颗粒发育造血重建:外周血中的绝对中性粒细胞计数需要连续3天达到或超过0.5×10^9细胞/L。 巨型造血造血重构:血小板计数必须超过20×10^9/L,并且连续7天不依赖血小板输血。
24周
graft-versus-host disease (GvHD)
大体时间:2 years
incidence and severity of acute (aGvHD) and chronic graft-versus-host disease (cGvHD) (aGvHD refer to Glucksberg Criteria and cGvHD refer to the National Institutes of Health Consensus)
2 years
transplant related mortality (TRM)
大体时间:2 years
cumulative incidence of transplant related mortality
2 years
Regimen related toxicity
大体时间:2 years
Number of participants with regimen related toxicity as assessed by CTCAE v5.0
2 years
veno-occlusive disease (VOD)
大体时间:2 years
incidence of veno-occlusive disease (VOD) events (refer to modified Seattle Criteria of VOD)
2 years
event-free survival (EFS)
大体时间:2 years
It is measured from the time of entry into this trial to the date of first event (relapse, death from any cause, or grade III-IV acute GVHD); patients not known to have experienced any event at last follow-up are censored on the date they were last known to be event-free.
2 years
Cumulative incidence of relapse(CIR)
大体时间:2 years
It is measured the date from complete remission after transplantation to hematological relapse was recorded. Patients who had no relapse at the last follow-up were considered as censored data, and non-relapse death was regarded as a competing risk event.
2 years

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年6月1日

初级完成 (估计的)

2029年6月1日

研究完成 (估计的)

2030年6月1日

研究注册日期

首次提交

2026年5月2日

首先提交符合 QC 标准的

2026年5月2日

首次发布 (实际的)

2026年5月8日

研究记录更新

最后更新发布 (实际的)

2026年6月10日

上次提交的符合 QC 标准的更新

2026年6月8日

最后验证

2026年4月1日

更多信息

与本研究相关的术语

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

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