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

NCT07575412 | Not Yet Recruiting Phase 2

• 1 other identifier: 20260415030709179
• Study Type: interventional
• Target: 180
• 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 15-65 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Event-Free Survival (EFS)

  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.

  1 years

Secondary Outcomes (8)

• Overall survival（OS）

  2 years

• Cumulative incidence of relapse（CIR）

  2 years

• event-free survival (EFS)

  2 years

• transplant related mortality (TRM)

  2 years

• graft-versus-host disease (GvHD)

  2 years

Study Arms (2)

Experimental: SHR2554/AZA + Overlapped mBUCY

EXPERIMENTAL

Drug: SHR2554/AZA + Overlapped mBUCY

Active Comparator: mBUCY conditioning Regimen Group

ACTIVE COMPARATOR

Drug: mBUCY conditioning Regimen Group

Interventions

SHR2554/AZA + Overlapped mBUCY DRUG

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.

Experimental: SHR2554/AZA + Overlapped mBUCY

mBUCY conditioning Regimen Group DRUG

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

Active Comparator: mBUCY conditioning Regimen Group

Eligibility Criteria

• Age: 15 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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.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.

You may not qualify if:

• : 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.

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

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

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: May 2, 2026
• First Posted: May 8, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2030
• Last Updated: May 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)