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

NCT07562568 | Not Yet Recruiting Phase 2

• 1 other identifier: 20260414125804551
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

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

MDS; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; SHR2554; Azacytidine; Transplantation, Stem Cell; Conditioning Therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Time period for hematopoietic reconstruction

  24 weeks

• graft-versus-host disease (GvHD)

  2 years

• Overall survival（OS）

  2 years

• Disease-free survival（DFS）

  2 years

• transplant related mortality (TRM)

  2 years

Study Arms (2)

SHR2554/AZA + Overlapped TBF

EXPERIMENTAL

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

mBUCY conditioning Regimen Group

ACTIVE COMPARATOR

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

Interventions

SHR2554/AZA + Overlapped TBF COMBINATION_PRODUCT

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.

Also known as: Experimental Group

SHR2554/AZA + Overlapped TBF

mBUCY conditioning regimen DRUG

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.

Also known as: Control Group

mBUCY conditioning Regimen Group

Eligibility Criteria

• Age: 15 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• ECOG performance status 0-2.
• 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.
• Ability to understand the study and voluntary signed informed consent.

You may not qualify if:

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

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Control Groups

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Central Study Contacts

LIMIN LIU, MD

CONTACT

+86-512-6778183; Liminliu1006@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 26, 2026
• First Posted: May 1, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)