Venetoclax and Decitabin Based Conditioning Regimen Followed With Post-HSCT Decitabin Maintenance Therapy in TP53 Mutant AML/MDS Patients
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
This study aims to evaluate the effectiveness and safety of Venetoclax and Decitabin based conditioning regimen followed with post-HSCT Decitabin maintenance therapy in TP53 mutant AML/MDS Patients.
详细描述
In acute myeloid leukemia and myelodysplastic syndromes, TP53 gene mutation is a poor prognostic factor and a strong indication for hematopoietic stem cell transplantation. However, because of the high relapse rate of myeloid tumors with TP53 mutation, new comprehensive treatment is urgently needed to improve the efficacy of transplantation. Decitabin(DEC) has shown certain efficacy in primary patients with TP53 mutation, and Venetoclax (VEN) and DEC have synergistic effect. Based on this, we hypothesized that DEC and VEN should be added to the conditioning regimen in TP53 mutant AML/MDS patients in order to eliminate malignant clones with P53 mutation as much as possible, and intermittent DEC maintenance therapy should be used to prevent relapse after post-HSCT hematopoietic reconstruction. We intend to conduct a multicenter, single-arm clinical study to evaluate the efficacy and safety of this protocol.
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
- 12 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •AML or MDS diagnosed according to 2016 WHO criteria with TP53 mutation before enrollment;
- •Aged from 12 to 70 years;
- •The Eastern Cooperative Oncology Group (ECOG) performance score of 0-2;
- •Creatinine clearance rate ≥ 60 mL/min (according to Cockcroft-Gault formula);
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥ 3× upper limit of normal range (ULN), total bilirubin ≤ 2×ULN;
- •Left ventricular ejection fraction (LVEF) assessed by echocardiography (ECHO) ≥ 45%;
- •Life expectancy > 8 weeks;
- •Sign the informed consent voluntarily, understand and comply with all trial requirements.
排除标准
- •Active autoimmune diseases, such as SLE, rheumatoid arthritis, etc.
- •Current active cardiovascular disease with clinically significance, such as uncontrolled arrhythmias, uncontrolled hypertension, congestive heart failure, any grade 3 or 4 heart disease determined by the New York Heart Association (NYHA) functional classification, or a history of myocardial infarction within the 6 months prior to screening;
- •Other serious medical conditions (e.g., advanced infection) that may limit the patient's participation in the trial;
- •Known human immunodeficiency virus (HIV) infection, or drug-uncontrolled chronic infection of hepatitis B virus (HBV-DNA > 1000IU/ml) or hepatitis C virus (anti-HCV positive);
- •Pregnant or lactating women;
- •Fail to understand, comply with the study protocol or sign the informed consent form.
研究组 & 干预措施
VEN and DEC based conditioning regimen followed with post-HSCT DEC maintenance therapy
干预措施: VEN and DEC based conditioning regimen (Drug)
VEN and DEC based conditioning regimen followed with post-HSCT DEC maintenance therapy
干预措施: DEC (Drug)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: At Year 1
The time from transplantation to the occurrence of any of the following: 1. Death from any cause 2. Disease recurrence, defined as one of the following: Leukemia blasts reappeared in peripheral blood, or blasts ≥ 5%, naive monocytes ≥ 5% in bone marrow, or extramedullary lesions.
次要结局
- Adverse effects(through study completion, an average of 1 year)
- Overall survival (OS)(At Year 1)
- Non-relapse mortality (NRM)(At Year 1)
- Cumulative relapse rate(At Year 1)
- Chronic graft-versus-host disease (GVHD)(through study completion, an average of 1 year)
- Acute graft-versus-host disease (GVHD)(At Day 100)
研究者
He Huang
Professor
Zhejiang University