A Single Arm, Phase 2 Study Evaluating Safety and Efficacy of Maintenance Therapy With Hypomethylating Agent and Venetoclax After Allogeneic Stem Cell Transplantation in Patients With f High-risk Myeloid Malignancies.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Leukemia-free survival (LFS) time
研究概览
简要总结
The main objective of the study is to evaluate the efficacy and safety of maintenance therapy with hypomethylating agent and Venetoclax to improve leukemia free survival for high-risk myeloid malignancies after allogeneic hematopoietic stem cell transplantation .
详细描述
This is a prospective single-arm study. Patients with high-risk AML or MDS aged between 18-70 years old will enroll in the study. They will be given hypomethylating agents (azacytidine 32mg/m2 or decitabine 5mg/m2) for 5 days and venetoclax 400mg/d for 7 days after allogeneic hematopoietic stem cell transplantation. The maintenance therapy will start from 60th days posttransplant, repeated every 28 days until up to 1-year posttransplant. The 1-year leukemia-free survival rate，1-year cumulative recurrence rate, and 1-year overall survival will be analyzed.
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with AML or MDS and have received allogeneic hematopoietic cell transplantation;
- •Patients with AML must have one of the following high-risk factors: Cytogenetics and molecular features consistent with adverse risk group by European LeukemiaNet classification for AML； require more than 2 courses of induction chemotherapy to reach complete remission； Extramedullary myeloid malignancy；≥CR2； Presence of measurable residual disease at the time of HSCT. *
- •Patients with MDS must have one of the following high-risk factors: IPSS-R scores are high-risk or very high-risk； Presence of TP53 mutation； Presence of measurable residual disease at the time of HSCT. *
- •CBC: ANC ≥ 1.0 × 10e9/L, Hb ≥ 80g/L, and PLT ≥ 50 × 10e9/L；
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or
- •Presence of measurable residual disease at the time of HSCT is defined as the following: Blast percentage in bone marrow detected by flow cytometry ≥0.01%； Presence of fusion gene or mutated gene by qPCR.
排除标准
- •Concurrent use of targeted drugs ;
- •Resistant to Venetoclax before transplantation;
- •Allergic to decitabine , Azacitidine or venetoclax;
- •Active grade II or higher acute GVHD ;
- •Active moderate or severe chronic GVHD ;
- •Diseases recurrence (abnormal myeloid cells detected by flow cytometry >0.01%, presence of WT1 or other genes, or extramedullary malignancy ), percentage of donor cells in bone marrow <90% or graft rejection:
- •CBC: ANC < 1.0 × 10e9/L, or PLT < 50 × 10e9/L；
- •Severe organ dysfunction: Elevated Aspartate transaminase (AST) /alanine transaminase (ALT), or direct bilirubin >3 times upper limit of normal; Creatinine clearance (Ccr)<50mL/min or serum creatinine >1.5 times upper limit of normal, whether hemodialysis treatment is performed;
- •Active uncontrolled systemic fungal, bacterial, or viral infection
- •Pregnant or lactating women;
- •Other severe complications and not suitable judged by researchers.
研究组 & 干预措施
AZA-VEN maintenance
hypomethylating agents (azacytidine 32mg/m2 or decitabine 5mg/m2) for 5 days and venetoclax 400mg/d for 7 days, repeated every 28 days until up to 1-year posttransplant.
干预措施: Venetoclax (Drug)
AZA-VEN maintenance
hypomethylating agents (azacytidine 32mg/m2 or decitabine 5mg/m2) for 5 days and venetoclax 400mg/d for 7 days, repeated every 28 days until up to 1-year posttransplant.
干预措施: Azacitidine or decitabine (Drug)
结局指标
主要结局
Leukemia-free survival (LFS) time
时间窗: From the date of transplantation, assessed up to 1 year after transplantation.
Summary statistics for LFS time will be computed for all patients.
次要结局
- Cumulative incidence of relapse(From the date of transplantation, assessed up to 1 year after transplantation.)
- Overall survival(From the date of transplantation, assessed up to 1 year after transplantation.)
- Incidence of toxicity of the regimen(From the date of transplantation, assessed up to 1 year after transplantation.)
研究者
Liping Wan
Associate Director of Department of Hematology
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine