Comparing standard-dose and intermediate-dose cytarabine for treating acute myeloid leukemia with RUNX1-RUNX1T1 fusion

Anthracycline-based Standard-dose vs Intermediate-dose Cytarabine Induction in the Treatment of Acute Myeloid Leukemia With RUNX1-RUNX1T1: a Prospective, Randomized, Controlled Phase III Clinical Trial

This study is testing if using a higher dose of cytarabine can help adults with acute myeloid leukemia who have a specific gene fusion feel better and achieve remission compared to the standard dose.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 14 Years to 60 Years
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT06744504 on ClinicalTrials.gov

What this trial studies

This phase III clinical trial aims to evaluate the effectiveness of standard-dose versus intermediate-dose cytarabine induction therapy in adult patients with acute myeloid leukemia (AML) who express the RUNX1-RUNX1T1 fusion gene. Eligible participants will be randomly assigned to receive either standard or intermediate doses of daunorubicin and cytarabine. The study will assess the rates of complete remission after induction therapy and the subsequent need for consolidation therapy. Patients who do not achieve remission after two cycles will be withdrawn from the treatment protocol. The trial seeks to determine if the intermediate-dose regimen can improve outcomes without increasing treatment-related mortality.

Who should consider this trial

Good fit: Ideal candidates are adults aged 14 to 60 with AML conforming to WHO criteria and possessing the RUNX1-RUNX1T1 fusion gene.

Not a fit: Patients who do not express the RUNX1-RUNX1T1 fusion gene or those who do not meet the inclusion criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved remission rates and survival outcomes for patients with AML expressing the RUNX1-RUNX1T1 fusion gene.

How similar studies have performed: Previous studies have shown varying success with different dosing strategies in AML treatment, but this specific comparison of standard versus intermediate doses in RUNX1-RUNX1T1 positive patients is novel.

Eligibility criteria

Inclusion Criteria:

1. AML conforming to WHO (2022) or ICC standards
2. Possessing the RUNX1::RUNX1T1 fusion gene
3. Age ranging from 14 to 60 years old, regardless of gender.
4. The performance status assessment of the Eastern Cooperative Oncology Group (ECOG-PS) being 0 - 2.
5. Meeting the requirements of the following laboratory examination indicators (conducted within 7 days before treatment):

1\) Total bilirubin ≤ 1.5 times the upper limit of the normal value for the same age group; 2) AST and ALT ≤ 2.5 times the upper limit of the normal value for the same age group; 3) Serum creatinine \< 2 times the upper limit of the normal value for the same age group; 4) Cardiac enzymes \< 2 times the upper limit of the normal value for the same age group; 5) The cardiac ejection fraction determined by echocardiography (ECHO) \> 50%. An informed consent form must be signed before the commencement of all specific research procedures, either by the patient themselves or their immediate relatives. Considering the patient's condition, if the patient's signature is not conducive to the treatment of the disease, the informed consent form shall be signed by the legal guardian or the immediate relatives of the patient.

Exclusion Criteria:

1. Acute promyelocytic leukemia accompanied by PML-RARA fusion gene.
2. Acute myeloid leukemia featuring BCR-ABL fusion gene.
3. Patients undergoing retreatment (but can receive cytoreductive therapy with hydroxyurea and cytarabine).
4. Individuals concurrently having malignant tumors in other organs (requiring treatment).
5. Active cardiac disorders, defined as one or more of the following:

1\) A history of uncontrolled or symptomatic angina pectoris; 2) Myocardial infarction less than 6 months from study enrollment; 3) A history of significant arrhythmia requiring medication or presenting with severe clinical symptoms; 4) Uncontrolled or symptomatic congestive heart failure (\> NYHA Class 2)

6\. Severe infectious diseases (untreated tuberculosis, pulmonary aspergillosis).

7\. Individuals deemed ineligible for enrollment by the investigator.

Where this trial is running

Tianjin, Tianjin Municipality

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

Study contacts

• Study coordinator: Hui Wei, MD

Conditions AML; RUNX1-RUNX1T1 Fusion Protein Expression