FLT3-ITD Targeted Therapy in Fit AML Patients

NCT07425808 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: EORTC 2467-LG
• Study Type: interventional
• Target: 230
• Locations: 0 countries
• Sites: N/A

Brief Summary

This international, multicenter, randomized (1:1), open-label phase II/III trial will evaluate the efficacy and safety of gilteritinib combined with azacitidine and venetoclax (experimental arm) versus standard "7+3" induction plus a FLT3inhibitor (quizartinib or midostaurin) (control arm) in newly diagnosed FLT3-ITD mutated AML patients eligible for intensive chemotherapy.

Conditions

AML (Acute Myeloid Leukemia)

Outcome Measures

Primary Outcomes (2)

• Phase II: Achievement of CR/CRi documented within 6 months from randomization, occurring prior to allografting and before initiation of any post-protocol treatments.

  The European LeukemiaNet (ELN) 2022 criteria will be used to evaluate CR/CRi.

  Within 6 months from randomization

• Phase III: Overall survival

  From baseline through study completion, an average of 7 years

Secondary Outcomes (11)

• Achievement of CR/CRi documented within 6 months from randomization, occurring prior to allografting and before initiation of any post-protocol treatments (for the phase III component of the trial only)

  Within 6 months from randomization

• Overall survival (for the phase II component of the trial only)

  From baseline through study completion, an average of 7 years

• Event-free survival

  From baseline through study completion, an average of 7 years

• Incidence of adverse events

  From baseline through study completion, an average of 7 years

• Deterioration from baseline by ≥10 points in global health status measured by EORTC QLQ-C30

  Weeks 1, 2, 3, 4, 10, and month 6, 12, and 30 from randomization

Study Arms (2)

Triplet combination of venetoclax, azacitidine and gilteritinib

EXPERIMENTAL

Triplet regimen consisting of venetoclax, azacitidine and gilteritinib, administered for up to 12 cycles (28-day cycles). This will be followed by up to 12 additional cycles of azacitidine in combination with gilteritinib (28-day cycles).

Drug: Gilteritinib; Drug: Venetoclax; Drug: Azacitidine (AZA)

Local standard of care

ACTIVE COMPARATOR

Local standard of care, consisting of induction with '7+3', consolidation with high-dose cytarabine, and maintenance with a FLT3 inhibitor (midostaurin, quizartinib, or sorafenib) as per local practice.

Drug: Local standard of care (SOC)

Interventions

Venetoclax DRUG

Cycle 1: ramp-up from 100mg on day 1, 200 mg on day 2 and 400 mg on days 3 - 28. Cycle 2 - 12: venetoclax 400 mg once daily orally days 1-7.

Triplet combination of venetoclax, azacitidine and gilteritinib

Azacitidine (AZA) DRUG

Cycle 1: 75 mg/m² once daily subcutaneously on days 1-7. Cycle 2 -12: 75 mg/m² once daily subcutaneously on days 1-5. Cycle 13 - 24: 75 mg/m² once daily subcutaneously on days 1-5.

Triplet combination of venetoclax, azacitidine and gilteritinib

Local standard of care (SOC) DRUG

Local SOC is "7+3" + Midostaurin (100 mg) or Quizartinib (35.4 mg)

Local standard of care

Gilteritinib DRUG

Cycle 1: 80 mg once daily orally on days 1-28. Cycle 2 - 12: 80mg once daily orally on days 1-28. Cycle 13 - 24: gilteritinib 120 mg once daily orally on days 1-28. Following HSCT, maintenance with gilteritinib (120 mg once daily orally on days 1-28) will be offered for up to 36 cycles and started between day 30 and 90 after hematopoietic stem-cell transplantation (HSCT).

Triplet combination of venetoclax, azacitidine and gilteritinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed AML cytopathologically confirmed according to the 5th WHO classification
• Age between 18 and 75 years
• FLT3-ITD mutation as per local IVDR-compliant testing. Positivity is defined as a FLT3-ITD / FLT3-wild type (WT) ratio of ≥ 0.05 (5%))
• Eligibility for standard induction chemotherapy
• ECOG PS ≤ 2
• Adequate hepatic function (as indicated by total serum bilirubin level ≤2.5 x the institutional upper limit of normal range (UNL), unless due to Gilbert's syndrome, hemolysis or the underlying leukemia approved by the investigator; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤3 x UNL)
• Adequate renal function as defined by an eGFR ≥ 30 mL/min according to the 2021 CKD-EPI equation

You may not qualify if:

• Acute promyelocytic leukemia (APL)
• BCR-ABL positive leukemia or Ph1-positive chronic myeloid leukemia
• History of myeloproliferative neoplasm (MPN), including myelofibrosis, essential thrombocythemia, polycythemia vera
• Active central nervous system involvement by AML
• Active, uncontrolled infection (viral, bacterial or fungal): an infection controlled with an approved or closely monitored antibiotic/antifungal treatment is allowed.
• HIV, HBV or HCV active infection
• Grade \>3 CTCAE (v. 6) clinically relevant (as per local investigator) adverse events at the time of enrolment
• Prior treatment for myelodysplastic syndrome (MDS) with Venetoclax or hypomethylating agents (decitabine, azacitidine).
• Any prior AML therapies (except for emergency treatment with hydroxyurea or cytarabine for hyperleukocytosis) Note: Subjects who undergo diagnostic workup for APL and treatment with all-trans retinoic acid, but who are found not to have APL, are eligible (treatment with all-trans retinoic acid must be discontinued before starting induction chemotherapy).
• Any prior treatment with a FLT3 inhibitor
• Serious organ dysfunction as left ventricular ejection fraction \<40%, FEV1, FVC, DLCO (diffusion capacity) \<40% of predicted
• Cardiovascular disability status of New York Heart Association class ≥ 2
• Congenital long QT syndrome or QT Interval Corrected Using Fridericia's Formula (QTcF) \>450 msec Note: repeat electrocardiograms after correction of electrolytes or discontinuation of QT prolonging medications are allowed to meet entry criteria. In cases where QTcF \>450 msec is considered to be falsely increased due to inaccurate automated reading and not clinically significant (e.g. due to bundle branch block), patients are still eligible if cardiologist reviews and documents that QTcF is ≤ 450 msec when manually measured.
• Participant with a prior or concurrent malignancy or autoimmune disease requiring immunosuppressive therapy.
• Note: diseases whose natural history or treatment is not anticipated to interfere with the safety or efficacy assessment of the investigational regimen may be included only after discussion with the 2467 medical monitor and the study coordinator.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Fondazione GIMEMA: collaborator
• Astellas Pharma Inc: collaborator

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

gilteritinib; venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Christoph Rummelt, MD, PhD

  University Hospital Freiburg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

EORTC HQ

CONTACT

+32 2 774611; eortc@eortc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2026
• First Posted: February 23, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): February 1, 2032
• Last Updated: February 23, 2026

Record last verified: 2026-02