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

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.

Eligibility

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.

Conditions5

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