The Efficacy of Triple Regimen in Newly Diagnosed AML Patients With FLT3 Mutation
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age14+
SponsorInstitute of Hematology & Blood Diseases Hospital, China
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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).
Trial design
Design model
Parallel
Treatments tested in this trial
Venetoclax
DrugVenetoclax dose and schedule determined by arms and treatment phases
Cytarabine
DrugConsolidation 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
DrugGilteritinib 120mg schedule determined by arms or treatment phases
Azacitadine (AZA)
DrugAzacitidine 75mg/m2/d schedule determined by treatment phases
Treatment groups
66 Participants
are divided into 3 treatment groupsGroup A: Triple Regimen Induction of Arm1Experimental treatment 4 interventions
Group B: Triple Regimen Induction of Arm2Experimental treatment 4 interventions
Group C: Triple Regimen Induction of Arm3Experimental treatment 4 interventions
Trial outcomes
Primary outcomes
1
Composite 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 participants2
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 participants3
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 participants4
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 participantsSecondary outcomes
1
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 participants2
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 participants3
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 participants4
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 participantsSponsors and contacts
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Source ClinicalTrials.gov