Gilteritinib Plus VA Followed By Consolidation Chemotherapy in Newly Diagnosed FLT3-ITD+ AML

NCT07259707 | Recruiting Phase 2 DMC

• 1 other identifier: IIT20250133C
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial aims to evaluate whether molecular MRD-guided chemotherapy can effectively treat FLT3-ITD mutated AML and potentially replace allogeneic hematopoietic stem cell transplantation. It primarily seeks to answer:

• What is the complete remission rate after initial induction with Gilteritinib, Venetoclax, and Azacitidine?
• What are the survival rates and safety of subsequent high-dose cytarabine consolidation after two cycles of this induction therapy? As a single-arm study, outcomes will be compared against historical data from standard treatments (including transplant) to assess if the new strategy is equally or more effective. Participants will:
• Undergo three cycles of high-dose cytarabine consolidation after two cycles of induction therapy, contingent upon achieving deep FLT3-ITD molecular remission.
• Start Gilteritinib maintenance therapy after consolidation if FLT3-ITD remains detectable, continuing until deep molecular remission is achieved again.

Conditions

Acute Myeloid Leukemia; FLT3 Internal Tandem Duplication Positive; Intermediate Risk Acute Myeloid Leukemia; Fit Patients

Keywords

acute myeloid leukemia; FLT3-ITD; Intermediate Risk; Fit; Gilteritinib; Deep molecular remission

Outcome Measures

Primary Outcomes (1)

• Composite Complete Remission (CRc) Rate after 2 induction cycles

  CRc is defined as the proportion of participants achieving CR or CRi based on 2022 ELN criteria. CR: Bone marrow blasts \<5%, ANC ≥1.0 x 10⁹/L, platelets ≥100 x 10⁹/L, no extramedullary disease, and transfusion independence. CRi: Bone marrow blasts \<5%, no extramedullary disease, and insufficient hematologic recovery to qualify for CR.

  At day 28 of cycle 2 of GVA induction therapy (each cycle is typically 28 days with 2-weeks intervals).

Secondary Outcomes (7)

• MRD Negativity Rate

  At the time of CRc assessment (at day 28 of cycle 2).

• Deep Molecular Negativity Rate (for FLT3-ITD)

  At the time point for CRc assessment (at day 28 of cycle 2)

• Overall Survival (OS)

  follow up 24 months

• Leukemia-Free Survival (LFS)

  follow up 24 months.

• Molecular Free Survival (mLFS)

  follow up 24 months

Study Arms (1)

GVA + HDAC Consolidation + Gilteritinib Maintenance

EXPERIMENTAL

This is a single-arm study contains three phases: Phase I. Induction Therapy: Gilteritinib + Venetoclax + Azacitidine (GVA Regimen) for 2 cycles Phase II. Consolidation Therapy: Gilteritinib + High-Dose Cytarabine (HDAC) for 3 cycles Phase III. Maintenance Therapy: Gilteritinib monotherapy for up to 3 months

Drug: GVA + HDAC Consolidation & Gilteritinib Maintenance

Interventions

GVA + HDAC Consolidation & Gilteritinib Maintenance DRUG

Phase I. Induction Therapy (2 cycles): Gilteritinib plus 80 mg, orally (po), once daily (qd), continuously from Day 1 of Cycle 1 until the end of Induction.Venetoclax + Azacitidine (VA Regimen): Azacitidine: 75 mg/m², intravenously (iv) or subcutaneously (sc), once daily on Days 1-7 of each 28-day cycle.Venetoclax: Cycle 1: Dose ramp-up: 100 mg po on Day 1, 200 mg po on Day 2, then 400 mg po once daily from Day 3 to Day 28.Subsequent Cycles: 400 mg po once daily on Days 1-28 of each 28-day cycle. Phase II. Consolidation Therapy (3 cycles): High-Dose Cytarabine (HiDAC): 3.0 g/m², intravenously (iv), over 3 hours, every 12 hours (q12h) on Days 1, 3, and 5 (total of 6 doses per cycle)；Gilteritinib: Dose increased to 120 mg, orally (po), once daily (qd), from day8 to day21. The interval of each cycle is 30 days. Phase III. Maintenance Therapy: Gilteritinib: 120 mg, orally (po), once daily (qd), continuously for up to 3 months.

GVA + HDAC Consolidation + Gilteritinib Maintenance

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Each subject (or their legal representative) must sign an informed consent form (ICF) before any specific study procedures or tests, indicating that he/she understands the purpose and procedures of the study and is willing to participate.
• Age ≥ 18 years or reaching the legal minimum adult age (whichever is greater) and ≤ 60 years (at screening);
• Newly diagnosed acute myeloid leukemia with FLT3-ITD mutation according to the European LeukemiaNet (ELN) 2022 diagnostic criteria (no VAF requirement), with no low-risk or high-risk genetic features as defined by ELN 2022.
• ECOG performance status ≤ 2. Biochemical indicators must be within the following limits within 21 days before randomization and at baseline: ALT and AST ≤ 3× upper limit of normal (ULN); total bilirubin ≤ 3× ULN; serum creatinine ≤ 2× ULN or CrCl ≥ 40 mL/min. LVEF determined by echocardiography is within the normal range (LVEF \> 50%).

You may not qualify if:

• Diagnosed with acute promyelocytic leukemia (APL), BCR-ABL positive acute myeloid leukemia, or AML secondary to previous chemotherapy or radiotherapy.
• History of other malignancies, except for adequately treated non-malignant skin melanoma, cured in situ tumors, or other solid tumors that have been treated and have had no evidence of disease for at least 2 years.
• Assessed as unfit for intensive chemotherapy based on the following criteria: ECOG performance status ≥ 2 at screening; severe cardiac diseases (e.g., congestive heart failure requiring treatment, ejection fraction ≤ 50%, or chronic stable angina); severe pulmonary diseases (e.g., DLCO ≤ 65% or FEV1 ≤ 65%); creatinine clearance \< 45 ml/min (calculated by Cockcroft-Gault equation), liver disease with total bilirubin \> 1.5 times the normal upper limit (ULN); any other comorbidities deemed incompatible with intensive chemotherapy by the attending physician.
• Uncontrolled fungal, bacterial, or viral infections.
• Known active clinically relevant liver disease (e.g., active hepatitis B or C); known history of HIV infection (participants should undergo HIV testing before randomization).
• History of allergy to any excipients in gilteritinib tablets.
• Pregnant or breastfeeding women.
• Other conditions deemed unsuitable for this study by the investigator.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead

Study Sites (1)

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Jie Sun

CONTACT

+8613867439726; jsun1492@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Attending, Associated Professor

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: December 2, 2025
• Study Start: January 25, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: February 4, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)