Overview
This investigator-initiated, single-arm, phase II trial is aimed to evaluate the efficacy and safety of a venetoclax-based, anthracycline-free regimen in patients with newly diagnosed CBFβ::MYH11-positive acute myeloid leukemia.
Description
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.
Eligibility
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.
