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.
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: 1. To determine the overall response rate (ORR) of 2 cycles of VEN/HMA in patients with ND CBFβ::MYH11-positive AML. 2. To determine the safety of the combination regimen. 3. To study the trajectories of molecular measurable residual disease (MRD) during the therapy. 4. To evaluate the impact of baseline genomic alterations on response and survival of the combination regimen. 5. 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Given PO, once daily. Treatment in cycle 1, the dose is 100 mg on day 1, then ramp up to 400mg. In all subsequent cycles, the dose of venetoclax is initiated at 400 mg daily.
Given SC
Given IV
Ethical Committee of the First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China
The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology
Suzhou, Jiangsu, China
composite complete remission rate
CR/CRi rate will be determined.
Time frame: after 2 cycles of induction therapy with VEN/HMA (each cycle is 28 days).
Overall response rate (ORR)
ORR will be determined.
Time frame: after 2 cycles of induction therapy with VEN/HMA (each cycle is 28 days).
Incidence of adverse events
Safety profile based on NCI CTCAE version 5.0 will be determined.
Time frame: From the start of treatment until death or last follow-up, assessed for up to 3 years.
measurable residual disease (MRD) negativity
MRD will be assessed by real-time qRCR.
Time frame: From the start of treatment until death or last follow-up, assessed for up to 3 years.
Impact of concurrent gene mutations
The impact of concurrent gene mutations ( analysis via an 81-gene institutional next-generation sequencing platform) on response and the survival of the combination regimen will be assessed.
Time frame: Baseline
Overall survival (OS)
OS will be assessed.
Time frame: From the start of treatment until death or last follow-up, assessed for up to 3 years.
Event-free survival (EFS)
EFS will be assessed.
Time frame: up to 3 years.
Duration of response (DOR)
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Given IV
DOR will be assessed.
Time frame: up to 3 years.