Testing the Addition of Venetoclax or Gemtuzumab Ozogamicin (GO) to Usual Treatment Regimen (Cytarabine and Daunorubicin, "7+3") for Core Binding Factor Acute Myeloid Leukemia (CBF-AML) to Improve Response (A MYELOMATCH Treatment Trial)

Summary

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.

Detailed Description

PRIMARY OBJECTIVE: I. Compare the rates of complete remission (CR) without measurable residual disease (CRMRD-) by multiparameter flow cytometry following induction therapy between the two treatment arms in each cohort separately. SECONDARY OBJECTIVES: I. To compare the rates of CR and composite complete remission (CRc) (CR+complete remission with incomplete hematologic recovery \[CRi\]+complete remission with partial hematologic recovery \[CRh\]) between the treatment arms. II. To compare the overall survival (OS) between the treatment arms. III. To compare the event-free survival (EFS). IV. To compare the cumulative incidence of relapse (CIR). V. To compare the cumulative incidence of death (CID) between the treatment arms. VI. To compare the rate of early death at 30 days and 60 days between the treatment arms. VII. To assess the rate and frequency of adverse events between treatment arms. VIII. To evaluate mutant RAS and mutant KIT as predictive biomarkers for CRMRD- rate in CBF AML. EXPLORATORY OBJECTIVE: I. To compare MRD (and its clinical implication, e.g., relapse rates) between flow cytometry (FC) and next generation sequencing (NGS)-based (RUNX1::RUNX1T1 or CBFB::MYH11). CORRELATIVE OBJECTIVES: I. To evaluate the frequency and clinical impact of variant allele frequency (VAF) of KIT mutation, KIT mutations in different exons (e.g., exon 8 or 17), CD33 expression, additional (secondary) mutations and cytogenetic abnormalities. II. To evaluate the differences in clinical and molecular outcomes in patients with RUNX1::RUNX1T1 mutated versus CBFB::MYH11 mutated CBF AML. OUTLINE: Patients are randomized to 1 of 2 regimens. REGIMEN 1: Patients receive gemtuzumab ozogamicin intravenously (IV) on days 1 and 4, cytarabine IV, continuously, on days 1-7 and daunorubicin IV on days 1-3 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care consolidation/post-remission treatment at the discretion of the treating physician. Patients undergo echocardiography or multigated acquisition (MUGA) scan during screening and bone marrow aspiration and biopsy and blood sample collection throughout the study. Patients may also undergo optional buccal swab collection throughout the study. REGIMEN 2: Patients receive venetoclax orally (PO) once daily (QD) on days 1-11, cytarabine IV, continuously, on days 2-8 and daunorubicin IV on days 2-4 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care consolidation/post-remission treatment at the discretion of the treating physician. Patients undergo echocardiography or MUGA scan during screening and bone marrow aspiration and biopsy and blood sample collection throughout the study. Patients may also undergo optional buccal swab collection throughout the study. After completion of study treatment, patients are followed up at relapse and every 3 months for 2 years, then every 6 months until 5 years.

Eligibility Criteria

Interventions