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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
66
Venetoclax dose and schedule determined by arms and treatment phases
Consolidation therapy (3 courses): intermediate-dose cytarabine regimen :2g/m2 q12h d1-3, age \< 60 years;1g/m2 q12h d1-3, age ≥60 years. If NGS detected FLT3 mutation before consolidation chemotherapy, gilteritinib will be added during the consolidation course at d4-17.
Gilteritinib 120mg schedule determined by arms or treatment phases
Azacitidine 75mg/m2/d schedule determined by treatment phases
Blood Diseases Hospital
Tianjin, Tianjin Municipality, China
RECRUITINGComposite Complete remission (CRc) rate
The ratio of patients achieved CRc(CR/CRh/CRi) after induction therapy
Time frame: up to 3 months after the date of the last enrolled participants
Composite Complete remission (CRc) with negative MRD detected by flow cytometry.
The ratio of CRc with negative MRD detected by flow cytometry after induction, consolidation, and maintenance therapy.
Time frame: up to 1 years after the date of the last enrolled participants
To determine the tolerated dose of triple regimens
The dose of gilteritinib and venetoclax that can be safely combined with azacitidine
Time frame: up to 3 months after enrollment of the first participants
Event-free survival (EFS)
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.
Time frame: up to 2 years after the date of the last enrolled participants
CRc with negative MRD detected by NGS (next-generation sequencing)
The ratio of CRc with negative MRD detected by NGS after induction,consolidation, and maintenance therapy
Time frame: up to 1 years after the date of the last enrolled participants
overall survival
The interval from the date of enrollment to the date of death or the date of last follow-up, , whichever occurred first.
Time frame: up to 2 years after the date of the last enrolled participants
Relapse free survival
The interval from CR to the date of relapse, or the date of death, or the date of last follow-up, whichever occurred first. This outcome analyzes patients achieved CR in two courses of induction therapy.
Time frame: up to 2 years after the date of the last enrolled participants
30-day mortality
Percentage of patients who died within 30 days from enrollment
Time frame: Within 30 days of the date of the last enrolled participants
60-day mortality
Percentage of patients who died within 60 days from enrollment
Time frame: Within 60 days of the date of the last enrolled participants
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