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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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.
• Препарат 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

Первичные конечные точки

• Event-Free Survival (EFS) [Срок оценки: 1 years]

Вторичные конечные точки (8)

• Overall survival（OS） [Срок оценки: 2 years]
• Cumulative incidence of relapse（CIR） [Срок оценки: 2 years]
• event-free survival (EFS) [Срок оценки: 2 years]
• transplant related mortality (TRM) [Срок оценки: 2 years]
• graft-versus-host disease (GvHD) [Срок оценки: 2 years]
• Time period for hematopoietic reconstruction [Срок оценки: 24 weeks]
• Regimen related toxicity [Срок оценки: 2 years]
• veno-occlusive disease (VOD) [Срок оценки: 2 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of Soochow University — Сучжоу

Идентификаторы

NCT: NCT07575412 · 20260415030709179

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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