Clinical trial · Interventional
SHR2554/AZA + Overlapped TBF for High-risk/Relapsed Leukemia/MDS
A Prospective, Multicenter, Open-label, Randomized Controlled Trial of SHR2554 Plus Azacitidine in Overlapped Sequential Combination With TBF Conditioning Regimen in Patients With High-risk or Relapsed/Refractory Acute Leukemia and Myelodysplastic Neoplasms
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This study was designed as a prospective, multicenter, open-label, randomized controlled trial. Eligible participants were patients aged 15-60 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 TBF conditioning regimen, whereas the control group received the mBuCy conditioning regimen, both followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). The primary endpoint was the 2-year cumulative incidence of relapse (CIR) after allo-HSCT. Secondary endpoints included 2-year overall survival (OS), 2-year disease-free survival (DFS), transplant-related mortality (TRM), the incidence of acute and chronic graft-versus-host disease (GVHD), and safety profiles.
Conditions
Conditions (7)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Acute Lymphoblastic Leukemia | Acute Lymphoblastic Leukemia | ONTOLOGY_EXACT | 0.98 |
| Acute Myeloid Leukemia | Acute Myeloid Leukemia | CURATED_BROADER | 0.80 |
| Azacytidine | — | UNRESOLVED | — |
| Conditioning Therapy | — | UNRESOLVED | — |
| MDS | Myelodysplastic Syndrome | CURATED_BROADER | 0.80 |
| SHR2554 | — | UNRESOLVED | — |
| Transplantation, Stem Cell | — | UNRESOLVED | — |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| mBUCY conditioning regimen | Drug | — | UNRESOLVED |
| SHR2554/AZA + Overlapped TBF | Combination Product | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- SHR2554/AZA + Overlapped TBF
- description
- SHR2554 350 mg BID and azacitidine 75 mg/m² daily on days -9 to -3, overlapping with TBF conditioning: thiotepa 5 mg/kg on days -8 and -7; cytarabine 2 g/m² q12h on day -6; busulfan 0.8 mg/kg q6h on days -5, -4, -3 (total 3.2 mg/kg/day); fludarabine 30 mg/m²/day on days -6 to -2.
- interventionNames
- Combination Product: SHR2554/AZA + Overlapped TBF
- type
- ACTIVE_COMPARATOR
- label
- mBUCY conditioning Regimen Group
- description
- 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.
- interventionNames
- Drug: mBUCY conditioning regimen
Primary outcomes (1)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 15 Years
- Maximum age
- 60 Years
Show eligibility criteria text
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 Zeprumetostat, 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.
References
Publications (0)
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