MAC vs RIC for Transplantation in FLT3-ITD-Mutated AML Guided by UHS-NGS MRD ( FLT3 - MAC vs RIC )

Ki vehet részt

• Age between 18 to 60 years, any gender
• Diagnosis of AML according to WHO criteria
• Presence of FLT3-ITD mutation at diagnosis
• In first complete remission
• Planned first allogeneic hematopoietic stem cell transplantation using peripheral blood stem cells
• Planned post-transplant maintenance therapy with a FLT3 inhibitor (including sorafenib or gilteritinib)
• FLT3-ITD UHS-NGS MRD < 0.001% at 14 to 28 days prior to transplantation
• Completion of routine pre-transplant assessments; in the investigator's judgment, the patient is able to complete the conditioning regimen, stem cell infusion, and study follow-up as planned
• HCT-CI score of 0 to 2; in the investigator's judgment, the patient is eligible for either MAC or RIC conditioning intensity
• ECOG performance status at 0 to 2
• Estimated survival time ≥ 6 months
• Major organ function meets the following requirements: ALT and AST ≤2.5 × ULN; Total bilirubin ≤1.5 × ULN; subjects with Gilbert syndrome or elevated indirect bilirubin due to documented inactive hemolysis may be enrolled at the investigator's discretion; eGFR ≥30 mL/min/1.73 m², and not receiving maintenance dialysis; LVEF ≥50%, or cardiac function status determined by the investigator to be adequate to tolerate the study treatment; No requirement for high-flow oxygen therapy or mechanical ventilation support at rest
• Blood pressure is well-controlled; systolic blood pressure <160 mmHg and diastolic blood pressure <100 mmHg at rest during the screening period; if receiving antihypertensive therapy, the dosage should be essentially stable prior to randomization
• Able to undergo assessments (including complete blood count, reticulocyte count, iron metabolism markers, adverse event monitoring, and transfusion records) as required by the protocol, and demonstrates good compliance
• Women of childbearing potential have a negative serum or urine pregnancy test; subjects of childbearing potential and their partners are willing to use effective contraceptive measures during the study and for the specified period following the last dose
• The subject or their legally authorized representative has signed a written informed consent form approved by the ethics committee prior to the implementation of any study-specific procedures

Ki nem vehet részt

• Prior allogeneic hematopoietic stem cell transplantation
• Achieved complete remission (CR) only after more than two cycles of induction therapy, or met the criteria for primary refractory AML
• Clear evidence of disease progression, relapse, or a need to immediately initiate new anti-tumor therapy prior to randomization, which could significantly impact the assessment of study endpoints
• Uncontrolled severe infection prior to randomization, including but not limited to: Sepsis or septic shock; Active invasive fungal infection; Bacterial or viral infection requiring escalation of broad-spectrum anti-infective therapy where the clinical condition remains unstable; Other severe infections deemed by the investigator to make the patient unsuitable for enrollment
• Concomitant high-risk cardiovascular or cerebrovascular conditions, including: Myocardial infarction, acute coronary syndrome, stroke, or transient ischemic attack within 6 months prior to randomization; Deep vein thrombosis, pulmonary embolism, or other clinically significant thromboembolic events within 6 months prior to randomization; New York Heart Association (NYHA) Class III-IV heart failure; Uncontrolled severe cardiac arrhythmia; Unacceptable thrombotic risk as determined by the investigator
• Participation in another interventional clinical trial involving treatment with an investigational drug or device within the 4 weeks prior to randomization, where the investigator determines that such participation might interfere with the results of this study
• Concurrent active malignancy; exceptions include: Malignancies that have been curatively treated with no evidence of recurrence within 5 years; Adequately treated basal cell carcinoma or squamous cell carcinoma of the skin; Treated carcinoma in situ determined by the investigator to have no impact on the study
• Uncontrolled hypertension, defined as resting systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg despite optimized antihypertensive therapy
• Gastrointestinal disorders significantly affecting oral drug absorption or adherence (e.g., persistent vomiting, short bowel syndrome, active severe diarrhea, or other conditions judged by the investigator to significantly affect drug exposure), or inability to tolerate post-transplant FLT3 inhibitor maintenance therapy as determined by the investigator
• Presence of uncontrolled psychiatric disorders, cognitive impairment, substance abuse, or other conditions that could affect informed consent, adherence, or safety follow-up
• Any other medical, laboratory, or social factors that, in the investigator's opinion, could increase the risk to the subject, affect study adherence, or interfere with the assessment of efficacy or safety
• Active central nervous system (CNS) leukemia
• Pregnant or lactating women, or individuals unwilling to use effective contraceptive measures