SHR2554/AZA + Overlapped Modified BUCY for High-risk/Relapsed Leukemia/MDS
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
研究概览
地位
研究类型
注册 (估计的)
阶段
- 阶段2
联系人和位置
学习联系方式
- 姓名:LIMIN LIU, MD
- 电话号码:+86-512-6778183
- 邮箱:Liminliu1006@163.com
学习地点
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Jiangsu
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Suzhou、Jiangsu、中国、215006
- The First Affiliated Hospital of Soochow University
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参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
Inclusion Criteria:
- Age 15-60 years, of either sex.
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.
- 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
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 |
|---|---|
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实验性的:Experimental: SHR2554/AZA + Overlapped mBUCY
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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.
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有源比较器:Active Comparator: mBUCY conditioning Regimen Group
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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
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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 |
|---|---|---|
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Event-Free Survival (EFS)
大体时间:1 years
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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.
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1 years
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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总生存期(OS)
大体时间:2年
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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。
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2年
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造血重建的时间段
大体时间:24周
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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。
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24周
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graft-versus-host disease (GvHD)
大体时间:2 years
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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)
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2 years
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transplant related mortality (TRM)
大体时间:2 years
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cumulative incidence of transplant related mortality
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2 years
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Regimen related toxicity
大体时间:2 years
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Number of participants with regimen related toxicity as assessed by CTCAE v5.0
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2 years
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veno-occlusive disease (VOD)
大体时间:2 years
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incidence of veno-occlusive disease (VOD) events (refer to modified Seattle Criteria of VOD)
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2 years
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event-free survival (EFS)
大体时间:2 years
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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.
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2 years
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Cumulative incidence of relapse(CIR)
大体时间:2 years
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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.
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2 years
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合作者和调查者
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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