Study of A Venetoclax-based, Anthracycline-free Regimen in Newly Diagnosed CBFβ::MYH11(+) AML

Primary Objectives:

To determine the CR (complete remission) / CRi (complete remission with incomplete blood count recovery) rate of 2 cycles of VEN/HMA in patients with newly diagnosed (ND) CBFβ::MYH11-positive acute myeloid leukemia(AML).

Secondary Objectives:

• To determine the overall response rate (ORR) of 2 cycles of VEN/HMA in patients with ND CBFβ::MYH11-positive AML.
• To determine the safety of the combination regimen.
• To study the trajectories of molecular measurable residual disease (MRD) during the therapy.
• To evaluate the impact of baseline genomic alterations on response and survival of the combination regimen.
• To assess the duration of response, overall survival (OS) and event free survival (EFS) of patients.

OUTLINE:

INDUCTION:

Patients with newly diagnosed CBFβ::MYH11(+) AML receive 2 cycles of VEN/HMA as induction therapy. Venetoclax orally (PO) once daily (QD) on days 1-28, azacitidine subcutaneously (SC) on days 1-7 or decitabine intravenously (IV) over 30-60 minutes on days 1-5.

CONSOLIDATION:

Patient fitness will be reassessed according to the Ferrara criteria if CR or CRi is achieved after 2 cycles of VEN/HMA. Fit patients will receive four cycles of consolidation therapy with high-dose cytarabine (2g/m2 every 12 hours, on days 1-3) combined with venetoclax (on days 1-7). Unfit patients will continue to receive VEN/HMA until disease progression.

After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

Inclusion criteria

• Adults ≥ 18 years.
• Newly diagnosed CBFβ::MYH11(+) AML.
• Performance status 0-3 on the Eastern Cooperative Oncology Group (ECOG) Scale.
• Subject must voluntarily sign and date an informed consent, prior to the initiation of any screening or study-specific procedures.

Ferrara's criteria are used to determine whether a patient is unfit, and a patient is deemed unfit if at least one of the following criteria is met:

• Age>75 years.
• There are serious underlying heart, lung, kidney, liver complications.
• There are active infections that do not respond to anti-infective therapy.
• There is cognitive impairment.
• Other comorbidities that the doctor determines are not suitable for intensive chemotherapy.

Exclusion criteria

• Subject has received treatment with a hypomethylating agent and/or other chemotherapeutic agents either conventional or experimental or targeted drug therapy for AML (except oral hydroxyurea and/or leukocytometry to reduce white blood cell count).
• Pregnant or lactating women.
• To the knowledge of the subject and investigator, subject may not be able to complete all study visits or procedures required by the study protocol, including follow-up visits, and/or be unable to comply with the required study procedures.
• Other conditions deemed unsuitable for participation in this study by the investigator.