Maintenance Therapy With Selinexor and Azacitidine in TP53 Mutant AML/MDS After Transplantation

Daihong Liu

Status and phase: Active, not recruiting; Phase 1

Conditions: Allogeneic Hematopoietic Stem Cell Transplantation; TP53-mutated MDS and AML

Treatments: Drug: Maintenance Therapy with Selinexor and Azacitidine

Study type: Interventional

Funder types: Other

Identifiers

NCT07094464

S2025-055-01

Details and patient eligibility

About

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.

Full description

This research targets high-risk recurrence patients with TP53 mutations in AML/MDS, administering low-dose azacitidine combined with selinexor for maintenance treatment post-allo-HCT (Allogeneic Hematopoietic Cell Transplantation). The goal is to observe the safety and tolerability of this drug combination as maintenance therapy post-transplant. The primary outcome measure will be post-transplant recurrence rate and non-relapse survival rate, while secondary outcomes include overall survival and non-relapse mortality. Previous studies have indicated that azacitidine and selinexor are safe and effective in maintenance therapy for AML/MDS. This study aims to reduce the risk of recurrence and prolong disease-free survival.

Enrollment: 20 estimated patients

Sex: All

Ages: 14 to 75 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

Assigned Interventions

Experimental group

Description:

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.

Treatment:

Drug: Maintenance Therapy with Selinexor and Azacitidine