A Single-Arm, Open Phase I Clinical Study of Selinexor in Combination With Azacitidine for the Treatment of High-Risk AML/MDS Patients After Allo-HSCT

This study focuses on AML/MDS patients with TP53 mutations who are at high risk of relapse. Following allogeneic hematopoietic stem cell transplantation, low-dose azacitidine combined with selinexor is administered as maintenance therapy. The objective is to evaluate the safety and tolerability of the combination of azacitidine and selinexor as post-transplant maintenance treatment. The primary endpoints are post-transplant relapse rate and non-relapse mortality. The secondary endpoints are overall survival and non-relapse mortality. Previous studies have reported that azacitidine and selinexor are safe and effective as post-transplant maintenance therapy for AML/MDS. In this study, the two-drug combination is administered post-transplant with the aim of reducing the risk of relapse and prolonging disease-free survival.

• Azacitidine (AZA) Days 1 - 5 (Drug): azacitidine 35mg/m2
• Selinexor (Drug): selinexor 20mg q2w

Primary outcomes

• relapse free survival [1 year]: Relapse free survival (RFS) refers to the time from treatment to the first disease progression or death of the patient for any reason.

Secondary outcomes

• overall survival (OS) [1 year]: Overall survival (OS) refers to the time from the start of treatment to the death of the patient for any reason.
• event free survival (EFS) [1 year]: Event Free Survival (EFS) is a commonly used endpoint indicator in clinical trials to evaluate the survival time of patients without any adverse events during a specific time period. These adverse events include but are not limited to disease progression, death, treatment plan changes, and the occurrence of serious side effects
• Cumulative Incidence of Relapse, CIR [1 year]: Cumulative incidence of relapse (CIR) is the estimated probability of disease recurrence over time, calculated using a competing-risk model that accounts for non-relapse mortality as a competing event rather than censoring it.

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

1. Voluntary participation in the clinical study: The subject or their legal guardian fully understands the study, provides informed consent by signing the Informed Consent Form (ICF), and is willing to comply with and complete all trial procedures.
2. Age < 75 years at screening, regardless of gender.
3. Post-transplant MRD-negative acute myeloid leukemia / myelodysplastic syndrome with TP53 mutation.
4. No history of severe allergic constitution.
5. Liver function: ALT and AST ≤ 2.5 × upper limit of normal (ULN), and bilirubin ≤ 2 × ULN.
6. Renal function: Serum creatinine ≤ ULN.
7. No uncontrolled infection or severe psychiatric/psychological disorders.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-3, with an estimated life expectancy of ≥ 4 months.
9. Bone marrow flow cytometry confirming MRD negativity prior to enrollment.
10. Successful myeloid and platelet engraftment.
11. No active graft-versus-host disease (GVHD).

Exclusion Criteria:

* (1) Patients with known allergy or contraindications to the investigational drugs.

  (2) Pregnant or breastfeeding female patients.

  (3) Presence of uncontrolled active infection or active graft-versus-host disease (GVHD).

  (4) Patients with long-term smoking or heavy alcohol consumption that may interfere with the evaluation of trial results.

  (5) Patients with psychiatric disorders or other conditions that preclude obtaining informed consent, or who are unable to comply with treatment and examination procedures.

  (6) Patients who have undergone major organ surgery within less than 6 weeks prior to enrollment.

  (7) Abnormal liver function: ALT and AST > 2.5 × upper limit of normal (ULN), or bilirubin > 2 × ULN; abnormal renal function: serum creatinine > ULN.

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