Condition

• Acute Myeloid Leukemia

Eligibility

Eligible Ages

Over 60 Years

Eligible Sex

All

Accepts Healthy Volunteers

No

Criteria

Inclusion Criteria:

- Participants must have been registered to the MYELOMATCH Master Screening and
Reassessment Protocol prior to consenting to this study. Participants must have been
assigned to this clinical trial via MATCHBox prior to registration to this study.

- Note: Pre-enrollment/diagnosis labs must have already been performed under
MYELOMATCH

- Participants must have newly diagnosed, untreated acute myeloid leukemia (AML)
defined by

- Having ≥ 20% blasts in the bone marrow and/or peripheral blood or

- Having recurrent AML-specific genetic abnormalities with ≥ 10% blasts in the
bone marrow aspirate and/or peripheral blood

- Participants with acute promyelocytic leukemia (APL) with PML-RARA are not eligible

- Participants must not have FLT3 mutations (ITD or TKD)

- Participants must not have TP53 mutations

- Participants must not be receiving or planning to receive any other investigational
agents while on protocol therapy

- Participants must not have received prior therapy for AML, myelodysplastic syndrome
(MDS) or myeloproliferative neoplasm (MPN) with the exception of hydroxyurea,
all-trans retinoic acid (ATRA), BCR-ABL directed tyrosine kinase inhibitor,
colony-stimulating factors, erythropoiesis-stimulating agents, thrombopoietin
receptor agonist, lenalidomide, immunosuppressive therapy, intrathecal chemotherapy,
a cumulative dose of up to 1 g/m^2 of cytarabine, and/or leukapheresis, with a
maximum limit of 1 month of exposure

- Note: White blood cell (WBC) must be < 25 x 10^9/L prior to start of treatment.
Hydroxyurea, leukapheresis, and cytarabine ≤ 1g/m2 are permitted to control the
WBC prior to enrollment and initiation of protocol-defined therapy but must be
stopped prior to initiation of protocol therapy

- Participant must be ≥ 60 years old at the time of registration

- Participant must have been declared unfit for intensive therapy by the treating
physician at the time of registration to MYELOMATCH

- Participant must have Zubrod Performance Status of 0-3 within 28 days prior to
registration

- Participant must have a complete medical history and physical exam within 28 days
prior to registration

- Total bilirubin ≤ 3 x institutional upper limit of normal (ULN) unless history of
Gilbert's disease. Participants with history of Gilbert's disease must have total
bilirubin ≤ 5 x institutional ULN (within 28 days prior to registration)

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x institutional
ULN, unless considered elevated due to disease involvement (within 28 days prior to
registration)

- Participants must have a calculated creatinine clearance ≥ 30 mL/min using the
following Cockcroft-Gault Formula. This specimen must have been drawn and processed
within 28 days prior to registration. For creatinine clearance formula see the tools
on the CRA Workbench https://txwb.crab.org/TXWB/Tools.aspx

- Participants must have adequate cardiac function. Participants with known history or
current symptoms of cardiac disease, or history of treatment with cardiotoxic
agents, must have a clinical risk assessment of cardiac function using the New York
Heart Association Functional Classification. To be eligible for this trial,
participants must be class 3 or better

- Participants with a known history of human immunodeficiency virus (HIV)-infection
must be on effective anti-retroviral therapy at registration and have undetectable
viral load test on the most recent test results obtained within 6 months prior to
registration, if indicated

- Participants with a known history of chronic hepatitis B virus (HBV) infection must
have undetectable HBV viral load while on suppressive therapy on the most recent
test results obtained within 6 months prior to registration, if indicated

- Participants with a known history of hepatitis C virus (HCV) infection must have
been treated and cured. Participants currently being treated for HCV infection must
have undetectable HCV viral load test on the most recent test results obtained
within 6 months prior to registration, if indicated

- Participants must not have a prior or concurrent malignancy whose natural history or
treatment (in the opinion of the treating physician) has the potential to interfere
with the safety or efficacy assessment of the investigational regimen

- Participants must not be pregnant or nursing (nursing includes breast milk fed to an
infant by any means, including from the breast, milk expressed by hand, or pumped).
Individuals who are of reproductive potential must have agreed to use an effective
contraceptive method with details provided as a part of the consent process. A
person who has had menses at any time in the preceding 12 consecutive months or who
has semen likely to contain sperm is considered to be of "reproductive potential."
In addition to routine contraceptive methods, "effective contraception" also
includes refraining from sexual activity that might result in pregnancy and surgery
intended to prevent pregnancy (or with a side-effect of pregnancy prevention)
including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion,
and vasectomy with testing showing no sperm in the semen

- Participants must be able to swallow and retain oral medications and have no known
gastrointestinal disorders likely to interfere with absorption of oral medications

- Participants must have agreed to have specimens submitted for translational medicine
for MRD under MYELOMATCH.

- Enrollment to this treatment study requires prior enrollment into the
myeloMATCH Master Protocol (MYELOMATCH). Participants enrolled in MYELOMATCH
will submit bone marrow samples, peripheral blood samples, and buccal swabs to
the Molecular Diagnostics Network (MDNet), the Clinical Laboratory Improvement
Act (CLIA) laboratory network for myeloMATCH. Refer to MYELOMATCH for
submission requirements and directions.

- In addition to the MYELOMATCH specimens, there will be specimens obtained on
treatment for this substudy. These specimens will be derived from procedures
performed as part of standard assessments in the clinical care and management
of AML with material being sent to the MDNet laboratories as specified. After
performing the required tests on the specimens, the MDNet laboratories will
send the residual material for biobanking and future research. Therefore,
participants must be asked for their consent for the biobanking of specimens
for future unspecified research. Participants may refuse this, but it is
mandatory for sites to ask participants

- Participants must be offered the opportunity to participate in specimen banking

- NOTE: As a part of the OPEN registration process the treating institution's identity
is provided in order to ensure that the current (within 365 days) date of
institutional review board approval for this study has been entered in the system.

- Participants must be informed of the investigational nature of this study and
must sign and give informed consent in accordance with institutional and
federal guidelines.

- For participants with impaired decision-making capabilities, legally authorized
representatives may sign and give informed consent on behalf of study
participants in accordance with applicable federal, local, and Central
Institutional Review Board (CIRB) regulations

Recruiting Locations

Study Contact

Detailed Description

PRIMARY OBJECTIVES: I. To compare whether the proportion of participants with a measurable residual disease (MRD) negative complete remission (CR) at 180 days (6 months) is not more than 12% worse between participants randomized to venetoclax for 14 days versus 28 days per cycle (non-inferiority assessment). II. If 14 days of venetoclax is found to be non-inferior to 28 days, to test whether the proportion of participants with an MRD-negative CR at 180 days (6 months) after randomization is significantly higher in the 14 days per cycle compared to the 28-days per cycle (superiority assessment). SECONDARY OBJECTIVES: I. In each arm, to estimate the frequency and severity of toxicities. II. In each arm, to estimate CR rates, CR with incomplete count recovery (CRi) (CRi, with and without MRD) rates, event-free survival (EFS), relapse-free survival (RFS), and overall survival (OS) for each of the regimens. III. In each arm, to use the disease characteristics from MATCHBox to describe mechanisms of resistance (and disease sensitivity) across the treatment arms. IV. In each arm, to tabulate the number of cycles competed, percent of cycles with at least one dose reduction, and percent of cycles with at least one treatment delay at 180 days (6 months) after randomization. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive decitabine and cedazuridine (ASTX727) orally (PO) once daily (QD) on days 1-5 and venetoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or treatment discontinuation. Patients undergo bone marrow aspiration and blood sample collection throughout the study. ARM 2: Patients receive ASTX727 PO QD on days 1-5 and venetoclax PO QD on days 1-14 of each cycle. Cycles repeat every 28 days in the absence of disease progression or treatment discontinuation. Patients undergo bone marrow aspiration and blood sample collection throughout the study. After completion of study treatment, patients are followed up periodically for up to 5 years.