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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; MDS; Conditioning Therapy; Transplantation, Stem Cell; SHR2554; Azacytidine
• Intervention / Treatment: Drug: mBUCY conditioning regimen; Combination product: SHR2554/AZA + Overlapped TBF

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: LIMIN LIU, MD; Phone Number: +86-512-6778183; Email: Liminliu1006@163.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR2554/AZA + Overlapped TBF; 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.	Combination product: SHR2554/AZA + Overlapped TBF; SHR2554/AZA + Overlapped TBF conditioning Regimen and GVHD Prophylaxis of Haploid transplantation (Haplo-HSCT) and unrelated donor transplantation (UDT) : Cyclosporine A (CsA) + Mycophenolate mofetil dispersible tablets (MMF) + short-term low-dose methotrexate (MTX) + rabbit anti-human antithymocyte globulin (ATG) or GVHD Prophylaxis of Matched Sibling Donor Hematopoietic Stem Cell Transplantation (MSD-HSCT)：Cyclosporine A (CsA) + short-term low-dose methotrexate (MTX), then stem cells are infused into patient's blood.; Other Names: Experimental Group
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.	Drug: mBUCY conditioning regimen; mBUCY conditioning Regimen and GVHD Prophylaxis of Haploid transplantation (Haplo-HSCT) and unrelated donor transplantation (UDT): Cyclosporine A (CsA) + Mycophenolate mofetil dispersible tablets (MMF) + short-term low-dose methotrexate (MTX) + rabbit anti-human antithymocyte globulin (ATG) or GVHD Prophylaxis of Matched Sibling Donor Hematopoietic Stem Cell Transplantation (MSD-HSCT)：Cyclosporine A (CsA) + short-term low-dose methotrexate (MTX), then stem cells are infused into patient's blood.; Other Names: Control Group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of relapse（CIR）	It is measured the date from complete remission after transplantation to hematological relapse or molecular 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival（OS）	It is measured from the date of entry into this trial to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.	2 years
Time period for hematopoietic reconstruction	Granulogenetic hematopoietic reconstitution: The absolute neutrophil count in peripheral blood needs to reach or exceed 0.5×10^9 cells/L for 3 consecutive days. Megakaryotic hematopoietic reconstitution: platelet count needs to be more than 20×10^9/L and does not rely on platelet transfusion for 7 consecutive days.	24 weeks
graft-versus-host disease (GvHD)	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
Disease-free survival（DFS）	It is measured from the time from randomization to the first of relapse or death.	2 years
transplant related mortality (TRM)	cumulative incidence of transplant related mortality	2 years
Regimen related toxicity	Number of participants with regimen related toxicity as assessed by CTCAE v5.0	2 years
veno-occlusive disease (VOD)	incidence of veno-occlusive disease (VOD) events (refer to modified Seattle Criteria of VOD)	2 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: April 26, 2026
• First Submitted That Met QC Criteria: April 26, 2026
• First Posted (Actual): May 1, 2026

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 26, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Myeloid; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Investigative Techniques; Epidemiologic Research Design; Epidemiologic Methods; Research Design; Methods; Control Groups
• Other Study ID Numbers: 20260414125804551

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No