University of Kansas Medical Center

Condition

• Core Binding Factor Acute Myeloid Leukemia

Eligibility

Eligible Ages

Between 18 Years and 59 Years

Eligible Sex

All

Accepts Healthy Volunteers

No

Criteria

Inclusion Criteria:

- 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

- GENERAL MYELOMATCH CRITERIA: Participants must not receive any cytarabine-containing
therapy other than up to 1g of cytarabine, which is allowed for urgent
cytoreduction. Hydroxyurea, all-trans retinoic acid (ATRA), BCR-ABL directed
tyrosine kinase inhibitor, erythropoiesis-stimulating agent, thrombopoietin receptor
agonist and lenalidomide is allowed

- Diagnosis of AML with t(8;21)(q22;q22.1)/RUNX1::RUNX1T1 or AML with
inv(16)(p13.1q22) or t(16;16)(p13.1;q22)/CBFB::MYH11. No FLT3 mutation (these
patients should be considered for a FLT3-focused MYELOMATCH study)

- Secondary CBF-AML (e.g., prior pre-leukemic hematologic malignancy or history of
chemotherapy/radiation therapy) is allowed.

- No prior AML or MDS-directed therapy except for urgent treatment of leukocytosis
with leukapheresis, cytarabine, and hydroxyurea, Prior intrathecal chemotherapy for
central nervous system (CNS) involvement of AML is permitted

- Age 18-59 years

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3

- Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless patient has a history of
Gilbert syndrome and direct bilirubin is ≤ 1.5 x ULN)

- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/
alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3 x
upper limit of normal (ULN)

- Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73m^2

- Not pregnant and not nursing, because this study involves an investigational agent
whose genotoxic, mutagenic and teratogenic effects on the developing fetus and
newborn are unknown. Therefore, for women of childbearing potential only, a negative
urine or serum pregnancy test done ≤ 7 days prior to registration is required

- Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational regimen are eligible for this trial

- Participants with CNS disease are eligible for this trial and will be treated
according to institutional guidelines with intrathecal chemotherapy for this aspect
of their disease

- Patients with known HIV infection on effective anti-retroviral therapy with
undetectable viral load within 6 months prior to registration are eligible for this
trial

- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated

- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load

- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better

- No known medical condition causing an inability to swallow oral formulations of
agents

Recruiting Locations

Study Contact

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.