A Single-Arm, Open-Label Phase I Clinical Study of Selinexor Combined With Azacitidine for Maintenance Therapy in TP53 Mutant AML/MDS Patients Post-Transplant
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Disease relapse
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(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.
排除标准
- •(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).
研究组 & 干预措施
Assigned Interventions
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.
- 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
- 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.
干预措施: Maintenance Therapy with Selinexor and Azacitidine (Drug)
结局指标
主要结局
Disease relapse
时间窗: 1 year after transplantation
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.
次要结局
- Drug-related adverse events(1 month after the last maintenance treatment ends)
- Progress-free survival (PFS)(1 year after transplantation)
- Non-relapse mortality (NRM)(1 year after transplantation)
- Measurable Residual Disease (MRD) in bone marrow(1 year after transplantation)
- Overall survival (OS)(1 year after transplantation)
研究者
Daihong Liu
Dr.
Chinese PLA General Hospital