Inclusion Criteria:
* Male and female ≥ 18 years of age.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Subjects with pathologically documented AML that has failed standard treatment, or subjects without prior therapy who refuse standard treatment options
* Bone marrow aspirate/biopsy results showing \>5% blasts
* WBC count \<25,000 cells/mm3 (25 x 109/L)
* Platelet count \>10,000 cells/mm3 (10 x 109/L)
* Adequate hepatic and renal function defined as:
* For Cohorts 1 and 2: serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤3.0 x upper limit of normal (ULN); for Cohort 3: ALT ≤2.5 or AST ≤2.5 ULN.
* Serum creatinine ≤2 mg/dL or Estimated Creatinine Clearance ≥30 mL/min (Cockcroft-Gault).
* Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin).
* PT/INR \<1.5 x ULN and PTT (aPTT) \<1.5 x ULN (When treated with warfarin or other vitamin K antagonists, then INR ≤3.0).
* Female subjects who are of non-reproductive potential (Female subjects of reproductive potential must have a negative serum pregnancy test upon study entry).
* Male and female subjects of reproductive potential agree to use highly effective methods of birth control (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], complete abstinence, or sterilized partner) during the period of therapy and for 90 days after the last dose of study drug.
Exclusion Criteria:
* Acute promyelocytic leukemia (French-American-British Class M3 AML).
* Known active central nervous system (CNS) leukemia.
* Known active systemic infection (Grade ≥2).
* Active bleeding disorders or clinical signs of bleeding (Grade ≥2).
* Prior bone marrow transplant that requires immunosuppressant therapy or presents with graft vs host disease (GVHD).
* History of other malignancies, except:
* Malignancy treated with curative intent and with no known active disease present for ≥3 years before the first dose of study drug and with low risk of recurrence by treating physician.
* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
* Adequately treated carcinoma in situ without evidence of disease.
* Prior treatment with a BTK inhibitor.
* For Cohort 3 subjects, prior treatment with hypomethylating agents (eg, azacitidine, decitabine)
* Anticancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal or any investigational therapy within 14 days or 5 half-lives (whichever is shorter) prior to first dose of study drug.
* Subject has received a monoclonal antibody for anticancer intent within 8 weeks prior to the first dose of study drug.
* Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
* Recent infection requiring intravenous (IV) systemic treatment that was completed ≤14 days before the first dose of study drug.
* Unresolved toxicities from prior anticancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4.03), Grade 0 or 1, unless otherwise defined in the inclusion/exclusion criteria with the exception of alopecia.
* Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia.
* History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
* Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV). Subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
* Major surgery within 4 weeks of first dose of study drug.
* Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
* Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
* Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
* Concomitant use of warfarin or other Vitamin K antagonists.
* Requires treatment or prophylaxis with a strong cytochrome P450 (CYP) 3A inhibitor
* Currently active, clinically significant hepatic impairment (≥ moderate hepatic impairment according to the Child Pugh classification).
* Lactating or pregnant.
* Unwilling or unable to participate in all required study evaluations and procedures.
* Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations).
