Efficacy of a triple drug regimen for newly diagnosed AML patients with FLT3 mutation

The Efficacy of a Triple Regimen Including Gilteritinib, Venetoclax, and Azacitidine in Newly Diagnosed Fit AML Patients With FLT3 Mutation

This study is testing a new combination of three drugs to see if it helps newly diagnosed acute myeloid leukemia patients with FLT3 mutations respond better to treatment.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 66 (estimated)
• Ages: 14 Years and up
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Drugs / interventions: chemotherapy, Gilteritinib
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT06561880 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of a triple induction regimen consisting of Gilteritinib, Venetoclax, and Azacitidine in newly diagnosed acute myeloid leukemia (AML) patients with FLT3 mutations who are fit for intensive chemotherapy. The study aims to determine the optimal dosage of Gilteritinib when combined with the other two drugs. Participants will undergo two courses of this triple regimen for induction, followed by consolidation therapy with cytarabine for those who achieve complete remission. The trial will monitor treatment response and minimal residual disease using advanced techniques to guide future treatment decisions.

Who should consider this trial

Good fit: Ideal candidates include newly diagnosed AML patients aged 15 and older with confirmed FLT3 mutations and an ECOG performance status of 0-2.

Not a fit: Patients with acute promyelocytic leukemia or those with specific genetic mutations like RUNX1-R may not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could significantly improve treatment outcomes and survival rates for patients with FLT3-mutated AML.

How similar studies have performed: Previous studies have shown promising results with FLT3 inhibitors in AML, indicating potential success for this novel combination approach.

Eligibility criteria

Inclusion Criteria:

1. 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.
2. Age ≥15 years old, male or female.
3. The physical status assessment (ECOG-PS) of the Eastern Oncology Collaboration group was 0-2 points.
4. Pass the requirements of the following laboratory tests (performed within 7 days before treatment) :

1\) 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.

Exclusion Criteria:

1. Acute promyelocytic leukemia with PML-RARA fusion gene
2. Acute myeloid leukemia with RUNX1-RUNX1T1 or CBFB-MYH11 fusion gene
3. Acute myeloid leukemia with BCR-ABL fusion gene
4. Have treated patients (those who have previously received induction chemotherapy but can receive hydroxyurea down-cell therapy).
5. Concurrent malignant tumors of other organs (those requiring treatment).
6. Active heart disease, defined as one or more of the following:

1\) A history of uncontrolled or symptomatic angina; 2) Myocardial infarction less than 6 months after enrollment; 3) Have a history of arrhythmia requiring drug treatment or severe clinical symptoms; 4) Uncontrolled or symptomatic congestive heart failure (\> NYHA level 2); 5) The ejection fraction is lower than the lower limit of the normal range. 7. Serious infectious diseases (uncured tuberculosis, pulmonary aspergillosis). 8. Those who were not considered suitable for inclusion by the researchers.

Where this trial is running

Tianjin, Tianjin Municipality

• Blood Diseases Hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Principal investigator: Hui Wei, doctor — Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
• Study coordinator: Hui Wei, Doctor

Conditions FLT3 Gene Mutation; AML