Clinical trial NCT06816134: Study on the Efficacy and Safety of the TmBU Conditioning Regimen in High-risk or Relapsed/Refractory Acute Leukemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Transplantation, Stem Cell
Conditioning Therapy
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2025-02-10
Enrollment: 48
Sex: ALL
Minimum age (years): 15
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Cumulative incidence of relapse（CIR）
timeFrame: 2 years
Secondary outcomes:
measure: Time period for hematopoietic reconstruction
timeFrame: 24 weeks
measure: Incidence of acute graft-versus-host disease (aGVHD)
timeFrame: 100 days
measure: Progressing-free survival（PFS）
timeFrame: 2 years
measure: Overall survival（OS）
timeFrame: 2 years
measure: Non-relapse mortality（NRM）
timeFrame: 2 years
measure: Graft-versus-host disease (GVHD)-free relapse-free survival (GRFS)
timeFrame: 2 years
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Sheng-Li Xue, M.D.
role: PRINCIPAL_INVESTIGATOR
References: