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

NCT06561880 | Recruiting Phase 1

• 1 other identifier: IIT2024055
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

FLT3 Gene Mutation; AML

Outcome Measures

Primary Outcomes (4)

• To determine the maximum tolerated dose of gilteritinib

  The maximum dose of gilteritinib that can be safely combined with azacitidine and venetoclax

  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.

  up to 2 years after the date of the last enrolled participants

• Complete remission (CR)/CR with partial hematologic recovery (CRh)/CR with incomplete hematologic recovery (CRi) with negative MRD detected by flow cytometry.

  The ratio of CR/CRh/CRi with negative MRD detected by flow cytometry after induction, consolidation, and maintenance therapy.

  up to 1 years after the date of the last enrolled participants

• CR/CRh/CRi with negative MRD detected by NGS (next-generation sequencing)

  The ratio of CR/CRh/CRi with negative MRD detected by NGS after induction,consolidation, and maintenance therapy.

  up to 1 years after the date of the last enrolled participants

Secondary Outcomes (5)

• CR/CRh/CRi rate

  up to 3 months after the date of the last enrolled participants

• overall survival

  up to 2 years 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

• 60-day mortality

  Within 60 days of the date of the last enrolled participants

Study Arms (1)

Triple Regimen Induction Including Gilteritinib, Venetoclax and Azacitidine

EXPERIMENTAL

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.

Drug: Gilteritinib; Drug: Cytarabine

Interventions

Gilteritinib 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.

Also known as: Venetoclax, Azacitidine

Triple Regimen Induction Including Gilteritinib, Venetoclax and Azacitidine

Cytarabine 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.

Also known as: Gilteritinib

Triple Regimen Induction Including Gilteritinib, Venetoclax and Azacitidine

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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) :
• \) 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Blood Diseases Hospital

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

Related Publications (3)

• 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.

  PMID: 38324741 BACKGROUND

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

  PMID: 37838437 BACKGROUND

• 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.

  PMID: 35884458 BACKGROUND

MeSH Terms

Interventions

gilteritinib; venetoclax; Azacitidine; Cytarabine

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Arabinonucleosides

Study Officials

• Hui Wei, doctor

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hui Wei, Doctor

CONTACT

13132507161; weihui@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2024
• First Posted: August 20, 2024
• Study Start: October 8, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): August 31, 2027
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)