- Participant must have histological confirmation of Acute Myeloid Leukemia (AML) by
World Health Organization criteria, be ineligible for intensive induction chemotherapy
and either be:
a. ≥ 75 years of age OR b. ≥ 18 to 74 years of age and fulfill at least one criteria
associated with lack of fitness for intensive induction chemotherapy: i. Eastern
Cooperative Oncology Group (ECOG) Performance status of 2 - 3; ii. Cardiac history of
Congestive Heart Failure (CHF) requiring treatment or Ejection Fraction ≤ 50% or
chronic stable angina; iii. Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)
≤ 65% or Forced Expiratory Volume in 1 second(FEV1) ≤ 65%; iv. Creatinine clearance ≥
30 mL/min to < 45 ml/min; v. Moderate hepatic impairment with total bilirubin > 1.5 to
≤ 3.0 × Upper Limit of Normal (ULN); vi. Other comorbidity that the physician judges
to be incompatible with conventional intensive chemotherapy which must be reviewed and
approved by the study medical monitor before study enrollment.
- Participant must have an ECOG Performance status:
1. of 0 to 2 for participants ≥ 75 years of age or
2. of 0 to 3 for participants between 18 to 74 years of age.
- Participant must have a projected life expectancy of at least 12 weeks.
- Participant must have adequate renal function as demonstrated by a creatinine
clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula or measured by
24-hours urine collection.
- Participant must have adequate liver function as demonstrated by:
1. aspartate aminotransferase (AST) ≤ 3.0 × ULN*
2. alanine aminotransferase (ALT) ≤ 3.0 × ULN*
3. bilirubin ≤ 1.5 × ULN*
- Subjects who are < 75 years of age may have bilirubin of ≤ 3.0 × ULN unless
considered to be due to leukemic organ involvement.
- Female participants must be either postmenopausal defined as:
1. Age > 55 years with no menses for 12 or more months without an alternative
2. Age ≤ 55 years with no menses for 12 or more months without an alternative
medical cause AND an FSH level > 40 IU/L; or
3. Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or
4. A Woman of Childbearing Potential (WOCBP) practicing at least one protocol
specified method of birth control starting at Study Day 1 through at least 180
days after the last dose of study drug.
- Male participants who are sexually active, must agree, from Study Day 1 through at
least 180 days after the last dose of study drug, to practice protocol specified
methods of contraception. Male subjects must agree to refrain from sperm donation from
initial study drug administration through at least 180 days after the last dose of
- Females of childbearing potential must have negative results for pregnancy test
1. At Screening with a serum sample obtained within 14 days prior to the first study
drug administration, and
2. Prior to dosing with urine sample obtained on Cycle 1 Day 1, if it has been > 7
days since obtaining the serum pregnancy test results.
3. Participants with borderline pregnancy tests at Screening must have a serum
pregnancy test ≥ 3 days later to document continued lack of a positive result.
- Participant must voluntarily sign and date an informed consent form, approved by an
Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the
initiation of any screening or study-specific procedures.
- Participant has received any prior treatment for AML with the exception of
hydroxyurea, allowed through the first cycle of study treatment. Note: Prior treatment
for Myelodysplastic Syndrome is allowed except for use of cytarabine.
- Participant had an antecedent myeloproliferative neoplasm (MPN) including
myelofibrosis, essential thrombocytosis, polycythemia vera, or chronic myelogenous
leukemia (CML) with or without BCR-ABL 1 translocation and AML with BCR-ABL 1
- Participants that have acute promyelocytic leukemia (APL).
- Participant has known Central Nervous System (CNS) involvement with AML.
- Participant has known Human Immunodeficiency Virus (HIV) infection (due to potential
drug-drug interactions between antiretroviral medications and venetoclax). HIV testing
will be performed at Screening, if required per local guidelines or institutional
- Participant is known to be positive for hepatitis B virus (HBV), or hepatitis C virus
(HCV) infection. Inactive hepatitis carrier status or low viral hepatitis titer on
antivirals (non-exclusionary medications) are not excluded.
- Participant has received strong or moderate CYP3A inducers 7 days prior to the
initiation of study treatment.
- Chinese participants are excluded from receiving strong and/or moderate CYP3A
inhibitors 7 days prior to the initiation of study treatment through the end of
intensive PK collection (24 hours post dose on Cycle 1 Day 10).
- Participant has consumed grapefruit, grapefruit products, Seville oranges (including
marmalade containing Seville oranges) or Star fruit within 3 days prior to the
initiation of study treatment.
- Participant has cardiovascular disability status of New York Heart Association Class >
Class 2 is defined as cardiac disease which subjects are comfortable at rest but ordinary
physical activity results in fatigue, palpitations, dyspnea, or angina pain.
Class 3 is defined as cardiac disease which subjects are comfortable at rest but less than
ordinary activity causes fatigue, palpitation, or dyspnea.
Class 4 is defined as cardiac disease which subjects have an inability to carry on any
physical activity without discomfort, symptoms of heart failure at rest, and if any
physical activity is undertaken then discomfort increases.
- Participant has chronic respiratory disease that requires continuous oxygen, or
significant history of renal, neurologic, psychiatric, endocrinologic, metabolic,
immunologic, hepatic, cardiovascular disease, any other medical condition or known
hypersensitivity to any of the study medications including excipients of LDAC that in
the opinion of the investigator would adversely affect his/her participating in this
- Participant has a malabsorption syndrome or other condition that precludes enteral
route of administration.
- Participant exhibits evidence of other clinically significant uncontrolled systemic
infection requiring therapy (viral, bacterial or fungal).
- Participant has a history of other malignancies prior to study entry, with the
1. Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of
2. Basal cell carcinoma of the skin or localized squamous cell carcinoma of the
3. Previous malignancy confined and surgically resected (or treated with other
modalities) with curative intent.
- Participant has a white blood cell count > 25 × 109/L. (Note: Hydroxyurea
administration or leukapheresis is permitted to meet this criterion).
- Previous treatment with venetoclax and/or current participation in any other research
study with investigational products.