The Efficacy of a Triple Regimen Including Gilteritinib, Venetoclax, and Azacitidine in Newly Diagnosed Fit AML Patients With FLT3 Mutation
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 66
- 试验地点
- 2
- 主要终点
- Complete remission (CR)/CR with partial hematologic recovery (CRh)/CR with incomplete hematologic recovery (CRi) with negative MRD detected by flow cytometry.
研究概览
简要总结
The FMS tyrosine kinase 3 (FLT3) gene mutation occurs in 30% of newly diagnosed AML patients, leading to a higher relapse rate and mortality rate. In the past, multi-drug combination chemotherapy regimens had limited efficacy in newly diagnosed AML patients with FLT3 mutations, especially in those with FLT3-ITD. However, the FLT3 inhibitors greatly improved the survival of AML patients with FLT3 mutations. Although several studies have focused on the effectiveness of FLT3 inhibitor combination therapy for FLT3-mutated AML, further studies are needed to determine the optimal regimen and dosage. A triple regimen consisting of Gilteritinib, Venetoclax, and Azacitidine had shown good efficacy in unfit newly diagnosed FLT3-mutated AML patients. This clinical trial aims to determine the optimal triple regimen and investigate its efficacy in newly diagnosed fit FLT3-mutated AML patients.
详细描述
This stuay intends to conduct a clinical study to explore the efficacy and safety of the triple induction regimen consisting of Gilteritinib, Venetoclax, and Azacitidine in newly diagnosed FLT3 mutated AML patients who are suitable for intensive chemotherapy. Patients will receive 2 courses of triple regimen therapy for induction and those who achieved complete remission will receive 3 courses of intermediate-dose cytarabine for consolidation. After consolidation therapy, dose-adjusted triple regimen therapy will be applied for 6 courses as maintenance treatment. Bone marrow morphology and minimal residual disease detected by flow cytometry and next-generation sequencing will be monitored during the treatment to provide evidence for treatment decisions. Response and survival of patients will be recorded to evaluate the efficacy of the triple regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •MDS/AML patients WHO meet AML and ICC definitions according to WHO (2022) or ICC standards (10%-20% of bone marrow naive cells) and have FLT3-TKD or ITD mutations detected by PCR or second-generation sequencing.
- •Age ≥15 years old, male or female.
- •The physical status assessment (ECOG-PS) of the Eastern Oncology Collaboration group was 0-2 points.
- •Pass the requirements of the following laboratory tests (performed within 7 days before treatment) :
- •1) Total bilirubin ≤ 1.5 times the upper limit of normal value (same age); 2) AST and ALT≤ 2.5 times the upper limit of normal value (same age); 3) Blood creatinine < 2 times the upper limit of normal (same age); 4) Myocardial enzymes < 2 times the upper limit of normal (same age); 5) Echocardiography (ECHO) was performed to determine the ejection fraction of the heart within the normal range.
排除标准
- •Acute promyelocytic leukemia with PML-RARA fusion gene
- •Acute myeloid leukemia with RUNX1-RUNX1T1 or CBFB-MYH11 fusion gene
- •Acute myeloid leukemia with BCR-ABL fusion gene
- •Have treated patients (those who have previously received induction chemotherapy but can receive hydroxyurea down-cell therapy).
- •Concurrent malignant tumors of other organs (those requiring treatment).
- •Active heart disease, defined as one or more of the following:
- •1) A history of uncontrolled or symptomatic angina; 2) Myocardial infarction less than 6 months after enrollment; 3) Have a history of arrhythmia requiring drug treatment or severe clinical symptoms; 4) Uncontrolled or symptomatic congestive heart failure (> NYHA level 2); 5) The ejection fraction is lower than the lower limit of the normal range.
- •Serious infectious diseases (uncured tuberculosis, pulmonary aspergillosis).
- •Those who were not considered suitable for inclusion by the researchers.
结局指标
主要结局
Complete remission (CR)/CR with partial hematologic recovery (CRh)/CR with incomplete hematologic recovery (CRi) with negative MRD detected by flow cytometry.
时间窗: up to 1 years after the date of the last enrolled participants
The ratio of CR/CRh/CRi with negative MRD detected by flow cytometry after induction, consolidation, and maintenance therapy.
To determine the maximum tolerated dose of gilteritinib
时间窗: up to 3 months after enrollment of the first participants
The maximum dose of gilteritinib that can be safely combined with azacitidine and venetoclax
Event-free survival (EFS)
时间窗: up to 2 years after the date of the last enrolled participants
The interval from the date of enrollment to the date of failed to achieve complete remission, the date of relapse, or the date of death, whichever occurred first.
CR/CRh/CRi with negative MRD detected by NGS (next-generation sequencing)
时间窗: up to 1 years after the date of the last enrolled participants
The ratio of CR/CRh/CRi with negative MRD detected by NGS after induction,consolidation, and maintenance therapy.
次要结局
- overall survival(up to 2 years after the date of the last enrolled participants)
- 60-day mortality(Within 60 days of the date of the last enrolled participants)
- CR/CRh/CRi rate(up to 3 months after the date of the last enrolled participants)
- Relapse free survival(up to 2 years after the date of the last enrolled participants)
- 30-day mortality(Within 30 days of the date of the last enrolled participants)