The Efficacy of Triple Regimen in Newly Diagnosed AML Patients With FLT3 Mutation

NCT ID: NCT06561880

Last Updated: 2025-10-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-08
• Study Completion Date: 2027-08-31

Brief Summary

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 dosage of the triple regimen and investigate its efficacy in newly diagnosed fit FLT3-mutated AML patients. Besides, this trial will provide evidence for treatment decisions based on measurable residual disease in patients with the triple regimen.

Detailed Description

This stuay intends to conduct a multi-center, single-arm clinical study to explore the efficacy of the triple induction regimen consisting of Gilteritinib, Venetoclax, and Azacitidine in newly diagnosed FLT3 mutated AML patients who are suitable for intensive chemotherapy. The maximum dose of Gilteritinib that can be safely combined with Azacitidine and Venetoclax will be determined. Patients will receive 2 courses of a 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.

Conditions

FLT3 Gene Mutation; AML

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Triple Regimen Induction Including Gilteritinib, Venetoclax and Azacitidine

Patients will receive 2 courses of induction with a triple regimen therapy consisting of Gilteritinib, Venetoclax, and Azacitidine. Patients who achieved complete remission will receive 3 courses of intermediate-dose cytarabine for consolidation. After consolidation therapy, dose-adjusted triple regimen therapy including Gilteritinib, Venetoclax, and Azacitidine will be applied for 6 courses as maintenance treatment.

Group Type: EXPERIMENTAL

Gilteritinib

Intervention Type: DRUG

Induction therapy regimen(2 courses):

triple regimen therapy: Azacitidine 75mg/m2/d d1-7; Venetoclax 100mg d1,200mg d2,400mg d3-28; Gilteritinib (as required at admission: 80 or 120mg) d1-28.

dose-adjusted triple regimen therapy: Azacitidine 75mg/m2/d d1-5; Venetoclax 400mg d1-7; Gilteritinib (as required at admission: 80 or 120mg) d1-28.

Patients with no remission after the first induction course will receive another course with triple regimen therapy; Patients with complete remission after the first induction course will receive another course of dose-adjusted triple regimen therapy.

Cytarabine

Intervention Type: DRUG

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

Intervention Type: DRUG

Maintenance treatment (6 courses):

dose-adjusted triple regimen therapy:Azacitidine 75mg/m2/d d1-5; Venetoclax 400mg d1-7; Gilteritinib (as required at admission: 80 or 120mg) d1-28.

Interventions

Gilteritinib

Induction therapy regimen(2 courses):

triple regimen therapy: Azacitidine 75mg/m2/d d1-7; Venetoclax 100mg d1,200mg d2,400mg d3-28; Gilteritinib (as required at admission: 80 or 120mg) d1-28.

dose-adjusted triple regimen therapy: Azacitidine 75mg/m2/d d1-5; Venetoclax 400mg d1-7; Gilteritinib (as required at admission: 80 or 120mg) d1-28.

Patients with no remission after the first induction course will receive another course with triple regimen therapy; Patients with complete remission after the first induction course will receive another course of dose-adjusted triple regimen therapy.

Intervention Type: DRUG

Cytarabine

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.

Intervention Type: DRUG

Gilteritinib

Maintenance treatment (6 courses):

dose-adjusted triple regimen therapy:Azacitidine 75mg/m2/d d1-5; Venetoclax 400mg d1-7; Gilteritinib (as required at admission: 80 or 120mg) d1-28.

Intervention Type: DRUG

Other Intervention Names

Venetoclax; Azacitidine; Gilteritinib; Venetoclax; Azacitidine

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Age ≥15 years old, male or female.

3. The physical status assessment (ECOG-PS) of the Eastern Oncology Collaboration group was 0-2 points.

4. 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.

Exclusion Criteria

1. Acute promyelocytic leukemia with PML-RARA fusion gene

2. Acute myeloid leukemia with RUNX1-RUNX1T1 or CBFB-MYH11 fusion gene

3. Acute myeloid leukemia with BCR-ABL fusion gene

4. Have treated patients (those who have previously received induction chemotherapy but can receive hydroxyurea down-cell therapy).

5. Concurrent malignant tumors of other organs (those requiring treatment).

6. 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. 7. Serious infectious diseases (uncured tuberculosis, pulmonary aspergillosis). 8. Those who were not considered suitable for inclusion by the researchers.

• Minimum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hui Wei, doctor

Role: PRINCIPAL_INVESTIGATOR

Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Locations

Blood Diseases Hospital

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Hui Wei, Doctor

Role: CONTACT

weihui@ihcams.ac.cn

13132507161

Facility Contacts

hui wei, MD

Role: primary

weihui@ihcams.ac.cn

86-13132507161

References

Wang ES, Goldberg AD, Tallman M, Walter RB, Karanes C, Sandhu K, Vigil CE, Collins R, Jain V, Stone RM. Crenolanib and Intensive Chemotherapy in Adults With Newly Diagnosed FLT3-Mutated AML. J Clin Oncol. 2024 May 20;42(15):1776-1787. doi: 10.1200/JCO.23.01061. Epub 2024 Feb 7.

Reference Type: BACKGROUND

PMID: 38324741 (View on PubMed)

Department of Error. Lancet. 2023 Oct 14;402(10410):1328. doi: 10.1016/S0140-6736(23)02235-3. No abstract available.

Reference Type: BACKGROUND

PMID: 37838437 (View on PubMed)

Knight TE, Edwards H, Meshinchi S, Taub JW, Ge Y. "FLipping" the Story: FLT3-Mutated Acute Myeloid Leukemia and the Evolving Role of FLT3 Inhibitors. Cancers (Basel). 2022 Jul 13;14(14):3398. doi: 10.3390/cancers14143398.

Reference Type: BACKGROUND

PMID: 35884458 (View on PubMed)

Other Identifiers

IIT2024055

Identifier Type: -

Identifier Source: org_study_id