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

Phase 1Active Not RecruitingNCT07094464

Daihong Liu20 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

TP53-mutated MDS and AML Allogeneic Hematopoietic Stem Cell Transplantation

Interventions

Maintenance Therapy with Selinexor and AzacitidineDRUG

1. Selinexor: Oral administration in 4 cycles: \- Dose Escalation Phase: 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 \- Dose Expansion: MTD/RP2D will be determined based on safety. 2. Azacitidine: 35 mg/m² for 5 days.

Eligibility

Sex: ALLMin age: 14 YearsMax age: 75 Years

Medical Language ↔ Plain English

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).

Locations (1)

Chinese PLA General Hospital

Beijing, Beijing Municipality, China

Outcomes

Primary Outcomes

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.