Study on the Efficacy and Safety of the TmBU Conditioning Regimen in High-risk or Relapsed/Refractory Acute Leukemia

A Prospective, Randomized Controlled Clinical Study on the Efficacy and Safety of the TmBU Regimen Versus mBUCY Regimen for Conditioning Before Allo-HSCT in High-risk or Relapsed/Refractory Acute Leukemia

This project is a prospective, single-center, randomized controlled clinical study. The subjects were high-risk or relapsed/refractory AML or ALL patients aged ≤ 65 years diagnosed by bone marrow cell morphology, immunology, genetics and therapeutic efficacy evaluation. The TmBU scheme or modified Bu/Cy (mBuCy) scheme was used for pretreatment in allo-HSCT. The primary endpoint of the study was the 2-year cumulative incidence of relapse (CIR) after allo-HSCT, and the secondary endpoints were 2-year overall survival rate (OS), progressing-free survival rate (PFS), non-relapse mortality rate (NRM), graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) rate.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Conditioning Therapy; Transplantation, Stem Cell
• Intervention / Treatment: Drug: TmBU conditioning Regimen; Drug: mBUCY conditioning regimen

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sheng-Li Xue, M.D.; Phone Number: 008651267781139; Email: slxue@suda.edu.cn

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: Sheng-Li Xue, M.D.; Phone Number: +8651267781139; Email: slxue@suda.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Confirmed diagnosis of AML or ALL according to WHO 2022 guideline criteria, with indications for allo-HSCT list below:

  1. Relapsed/primary refractory (definitions refer to NCCN 2025) or genetic high-risk group AML at diagnosis (risk stratification refers to ELN 2022)
  2. High-risk at diagnosis (risk stratification refers to ELN 2022) or MRD positive before transplantation B-ALL
  3. Confirmed diagnosis of T-ALL
  4. History of central nervous system leukemia (CNSL) or histopathologically confirmed extramedullary manifestation (EMD) during the course of the AML or ALL
• Age 15-65 years old (≤ 65 years old)
• HCT-CI score < 2 points ECOG 0-2 points

• Adequate organ function:

  1. Cardiac NYHA grade ≤ 2, left ventricular ejection fraction ≥55%
  2. Creatinine clearance ≥ 50ml/min
  3. ALT and AST ≤ 2.5 times the upper limit of the normal range, and total bilirubin ≤ 1.5 times the upper limit of the normal range
  4. Oxygen saturation > 92% without oxygen
• Expected survival time ≥ 3 months
• Ability to understand and voluntarily sign the informed consent form

Exclusion Criteria:

• With other malignant tumors and have received any treatment for this tumor within the past 3 years
• Previous or current other CNS disease (such as epilepsy, generalized seizure disorder, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis) or any CNS-related autoimmune disease
• HIV/Syphilis infection or uncontrolled active other infections (bacteria or fungus or virus is included)
• With active hepatitis B or hepatitis C infection
• Patients received cardiac angioplasty or stent implantation within 12 months before signing the informed consent form, or have symptoms requiring medical treatment for coronary heart disease
• With primary immunodeficiency or active autoimmune disease
• Previous history of severe immediate hypersensitivity reactions to any of the drugs to be used in this study
• Received a live vaccine within 6 weeks prior to screening
• Pregnant, lactating females and patients of childbearing potential who are unwilling to use contraception
• Inability to cooperate with the requirements of study, treatment and monitoring due to psychiatric illness or other conditions
• Patients not suitable for the study according to the investigator's assessment

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: TmBu conditioning Regimen Group; TmBU conditioning regimen（TT 7mg/kg -8~-7d; Ara-C 2g/m2/d -6d; CDA 5 mg/m2/d -6d; Bu 3.2 mg/kg/d from -5 to -3d）	Drug: TmBU conditioning Regimen; TmBU 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; mBuCy conditioning regimen（CCNU 250mg/m2/d -9d, Ara-C 2g/m2/d -8d; CDA 5 mg/m2/d -8d; Busulfan 3.2 mg/kg/d from -7 to -5 days; Cyclophosphamide 1.8 mg/m2/d from -4 to -3 days）	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
Incidence of acute graft-versus-host disease (aGVHD)		100 days
Progressing-free survival（PFS）	It is measured from the date of achievement of a remission until the date of relapse from CR, or CRi, or death from any cause; patients not known to have any of these events are censored on the date they were last examined.	2 years
Non-relapse mortality（NRM）	It is described as proportion of deaths due to non-primary recurrence from enrollment start date to 2 years post-transplant.	2 years
Graft-versus-host disease (GVHD)-free relapse-free survival (GRFS)	It is defined as a composite end point of death from any cause, relapse of malignancy, grade 3 to 4 acute GVHD, or chronic GVHD requiring systemic immune suppression therapy.	2 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Investigators: Principal Investigator: Sheng-Li Xue, M.D., The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2025
• Primary Completion (Estimated): January 30, 2028
• Study Completion (Estimated): January 30, 2030

Study Registration Dates

• First Submitted: February 4, 2025
• First Submitted That Met QC Criteria: February 4, 2025
• First Posted (Actual): February 10, 2025

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 19, 2026
• Last Verified: March 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: SZConditioning01

Drug and device information, study documents

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