This phase II MYELOMATCH treatment trial compares the effect of venetoclax to gemtuzumab ozogamicin, when given with cytarabine and daunorubicin ("7+3" regimen), for the treatment of patients with core binding factor acute myeloid leukemia (CBF-AML). Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Gemtuzumab ozogamicin is a monoclonal antibody, called gemtuzumab, linked to an antitumor antibiotic drug, called ozogamicin. Gemtuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD33 receptors, and delivers ozogamicin to kill them. Chemotherapy drugs, such as cytarabine and daunorubicin work in different ways to stop the growth of cancer cells either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax with cytarabine and daunorubicin may have fewer side effects and be as effective or better than the combination with gemtuzumab ozogamicin in treating patients with core binding factor AML.
GENERAL MYELOMATCH CRITERIA: Patients must be registered to the Master Screening and Reassessment Protocol, MYELOMATCH, and assigned to this protocol by the MATCHBox Treatment Verification Team
GENERAL MYELOMATCH CRITERIA: Participants must not have received prior anti-cancer therapy for AML or myelodysplastic syndrome (MDS)
Note: Hydroxyurea to control the white blood cell count (WBC) and cytarabine up to 1g for urgent cytoreduction is allowed.
Note: Prior erythroid stimulating agent (ESA) is not considered prior therapy for the purposes of eligibility
None
Parallel
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow aspiration
Cytarabine
DrugGiven IV
Daunorubicin Hydrochloride
DrugGiven IV
Echocardiography Test
Procedure/SurgeryUndergo echocardiography
Gemtuzumab Ozogamicin
DrugGiven IV
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA scan
Venetoclax
DrugGiven PO
Complete remission without measurable residual disease (CRMRD-)
MRD will be evaluated by Molecular Diagnostics Network flow cytometry and will be defined at a threshold of ≤ 10\^-3.
Rate of complete remission (CR)
Defined as the number of evaluable patients achieving a response of CR per European Leukemia Network (ELN) 2022 criteria at the end of treatment divided by the total number of evaluable patients. Rates of response will be compared between treatment arms using a chi-square test (or Fisher's exact test as needed). Point estimates will be generated for CR rate within each arm along with 95% confidence intervals using the Clopper-Pearson method.
Rate of composite CR
Defined as the number of evaluable patients achieving a response of CR or complete remission with incomplete hematologic recovery (CRi) or complete remission with partial hematologic recovery (CRh) per ELN 2022 criteria at the end of treatment divided by the total number of evaluable patients. Rates of response will be compared between treatment arms using a chi-square test (or Fisher's exact test as needed). Point estimates will be generated for CR rate within each arm along with 95% confidence intervals using the Clopper-Pearson method.
Overall survival (OS)
The distribution of OS will be estimated using method of Kaplan-Meier. The median OS and 95% confidence interval will be reported.
Event free survival (EVS)
Induction failure is defined as not achieving either CR, CRh or CRi by after induction therapy. The distribution of EFS will be estimated using method of Kaplan-Meier, and compared using log-rank tests. The median EFS and the corresponding 95% confidence interval will be reported.
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