CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

* (1) Voluntary participation in the clinical study: Participant or legal guardian understands and signs the Informed Consent Form (ICF) and is willing to comply with all trial procedures.

  (2) Age below 75 years at screening; gender not restricted. (3) Diagnosed with AML or MDS with TP53 mutation (VAF ≥ 2%) and post-allo-HCT. (4) No severe allergic constitution. (5) Liver function: ALT and AST ≤ 2.5 times the upper limit of normal, bilirubin ≤ 2 times the upper limit of normal.

  (6) Renal function: creatinine ≤ upper limit of normal. (7) No uncontrolled infections or severe psychiatric disorders. (8) ECOG performance score of 0-3; life expectancy of 4 months or more. (9) Peripheral blood counts for granulocytes and platelets.

Exclusion Criteria:

* (1) Patients with known allergies or contraindications to the study drugs. (2) Pregnant or breastfeeding women. (3) Patients with uncontrolled active infections or active GVHD. (4) Patients with a long history of smoking or alcohol abuse affecting trial outcome evaluation.

  (5) Patients with psychiatric disorders or conditions preventing informed consent, unable to comply with treatment and assessment requirements.

  (6) Patients who underwent major surgery on important organs less than 6 weeks prior.

  (7) Abnormal liver function: ALT or AST \> 2.5 times the upper limit of normal; bilirubin \> 2 times the upper limit of normal; renal function: creatinine \> upper limit of normal.

  (8) Patients deemed unsuitable for this clinical trial by the investigator (e.g., poor compliance, substance abuse).

主要终点：Disease relapse · The definition of disease relapse: After remission, patients present with one of the following three conditions: (1) ≥5% of primary lymphocytes and immature lymphocytes in the bone marrow; (2) Extramedullary leukemia occurs; (3) Leukemia cells were found in peripheral blood smears. The definition of MRD recurrence: Leukemia cells are detected by flow cytometry or molecular biology. · 1 year after transplantation
次要终点：Non-relapse mortality (NRM)；Overall survival (OS)；Progress-free survival (PFS)；Drug-related adverse events；Measurable Residual Disease (MRD) in bone marrow

• Assigned Interventions · EXPERIMENTAL · 1）Treatment will begin approximately 3 months post-transplant. The study duration will be 1 year with treatment cycles every 3 months, totaling 4 cycles. 1. Selinexor: Single-arm phase I study with sequential dose escalation of Selinexor. Three dose levels will be tested in separate cohorts: * Cohort 1: Selinexor, 20 mg, twice a week for 2 weeks * Cohort 2: Selinexor, 40 mg, twice a week for 2 weeks * Cohort 3: Selinexor, 60 mg, twice a week for 2 weeks 2. Azacitidine: 35 mg/m² for 5 days. 2）Bone marrow morphology, characteristic gene mutation or fusion gene quantification, immunophenotyping, chimerism, or transplant-related FISH will be assessed before and after each treatment cycle, according to the follow-up schedule post-transplant. Patients with hematological relapse at any time will discontinue from the experimental group and receive an alternative treatment.

This study aims to explore the safety and efficacy of selinexor combined with azacitidine for maintenance therapy in TP53 mutant AML/MDS patients following transplantation.