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

A Single-Center, Prospective, Single-Arm Phase II Clinical Study of Consolidation With High-Dose Cytarabine Following Deep Molecular Remission Induced by Gilteritinib Plus VA Regimen in Newly Diagnosed Intermediate-Risk Fit AML Patients With FLT3-ITD Mutation

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; FLT3 Internal Tandem Duplication Positive; Fit Patients; Intermediate Risk Acute Myeloid Leukemia
• Intervention / Treatment: Drug: GVA + HDAC Consolidation & Gilteritinib Maintenance

Detailed Description

This single-center, phase II trial evaluates a novel, transplant-sparing strategy for fit patients with newly diagnosed intermediate-risk acute myeloid leukemia (AML) harboring FLT3-ITD mutations. The central hypothesis is that achieving deep molecular remission-as measured by a highly sensitive assay termed "DeepScan" (Levis et al., Blood 2022)-can identify a subset of patients who may attain long-term survival without allogeneic hematopoietic stem cell transplantation (allo-HSCT).

The therapeutic strategy consists of a sequential three-phase approach:

Induction: Initial therapy combines the FLT3 inhibitor gilteritinib with venetoclax and azacitidine (the GVA regimen). This synergistic approach targets leukemia through concurrent inhibition of FLT3 and BCL-2 pathways, aiming to achieve high rates of complete remission and deep molecular clearance.

Consolidation: Patients who achieve deep FLT3-ITD negativity, as assessed by the "DeepScan" minimal residual disease (MRD) assay after induction therapy, will proceed to consolidation with high-dose cytarabine (2 g/m² twice daily for 3 days) for three cycles, concurrently with gilteritinib.

Maintenance: Patients maintaining deep FLT3-ITD negativity will receive gilteritinib monotherapy at 120 mg daily for 3 months. Those with detectable mutations will be withdrawn from the study.

A key innovation of this trial is the implementation of "DeepScan," a next-generation sequencing-based assay co-developed with Professor Levis's team. This method detects FLT3-ITD mutations with a sensitivity of up to 10-⁶, surpassing conventional MRD monitoring techniques. It is designed to accurately define a state of deep molecular remission, which serves as the primary biomarker for directing patients toward a transplant-free pathway.

This study challenges the current standard of care, in which allo-HSCT is frequently recommended. By prospectively assessing whether deep molecular responses-induced and maintained through this targeted and chemotherapy-inclusive regimen-can lead to durable survival, the trial aims to provide evidence for a paradigm shift in the treatment of FLT3-ITD-mutated AML, potentially offering a transplant-free alternative for selected patients.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jie Sun; Phone Number: +8613867439726; Email: jsun1492@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The First Affiliated Hospital, Zhejiang University School of Medicine
      • Contact: Jie Sun, MD,PH.D; Phone Number: +8613867439726; Email: jsun1492@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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%).

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: GVA + HDAC Consolidation + Gilteritinib Maintenance; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRD Negativity Rate	The proportion of participants who achieve CRc and subsequently achieve Measurable Residual Disease (MRD) negativity, defined as < 0.1% by multiparameter flow cytometry.	At the time of CRc assessment (at day 28 of cycle 2).
Deep Molecular Negativity Rate (for FLT3-ITD)	The proportion of participants who achieve deep molecular negative, defined as < 0.0001% (10^-6) via the DeepScan molecular assay, to the patients who achieved CRc	At the time point for CRc assessment (at day 28 of cycle 2)
Overall Survival (OS)	Time from enrollment to death from any cause, whichever came first (censored at last follow-up for survivors)	follow up 24 months
Leukemia-Free Survival (LFS)	Time from first composed complete remission to relapse or death, whichever occurred first	follow up 24 months.
Molecular Free Survival (mLFS)	The time from first deep molecular negative (FLT3-ITD < 0.0001%) to molecular relapse (above the 0.0001% threshold) or death from any cause	follow up 24 months
Cumulative Incidence of Relapse (CIR)	The cumulative probability of morphologic relapse, considering death without relapse as a competing risk.	follow up 24 months
Cumulative Incidence of Molecular Relapse (mCIR)	The cumulative probability of molecular relapse, defined as the re-emergence of FLT3-ITD at or above the 0.0001% threshold, to participants who achieved deep molecular negativity, considering death without molecular relapse as a competing risk.	follow up 24 months

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: November 21, 2025
• First Submitted That Met QC Criteria: November 21, 2025
• First Posted (Actual): December 2, 2025

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: acute myeloid leukemia; FLT3-ITD; Gilteritinib; Intermediate Risk; Fit; Deep molecular remission
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute
• Other Study ID Numbers: IIT20250133C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No