
    safety
  
['recurrent adult acute myeloid leukemia']
['cytarabine', 'ibrutinib', 'idarubicin']

        INCLUSION CRITERIA

          -  Previous morphologically-confirmed diagnosis of acute myeloid leukemia (AML) based on
             World Health Organization (WHO) Criteria

          -  At least one prior chemotherapy regimen to treat AML

          -  Disease relapse or refractory disease as shown by > 5% blasts in the bone marrow (not
             attributable to another cause). Administration of hydrea to control high WBC count is
             permitted.

          -  Age ≥ 18 years

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, or Karnofsky
             Performance Status (KPS) ≥ 60%

          -  Life expectancy > 4 weeks

          -  Platelet count ≥ 10,000/mm3 within 72 hours of initiating the Induction Cycle
             (platelet transfusion support is allowed)

          -  Serum creatinine ≤ 2.0 mg/dL within 72 hours of initiating the Induction Cycle

          -  Total bilirubin ≤ 2.1 mg/dL within within 72 hours of initiating the Induction Cycle
             (EXCEPTION: If elevation is not due to liver dysfunction, and is due primarily to
             elevated unconjugated hyperbilirubinemia secondary to Gilbert's syndrome, or hemolysis
             of non-hepatic origin)

          -  Serum glutamic oxaloacetic transaminase (SGOT) [aspartate aminotransferase (AST) ] ≤
             3.0 X upper limit of normal (ULN) within 72 hours of initiating the Induction Cycle

          -  Serum glutamic pyruvic transaminase (SGPT) [alanine aminotransferase (ALT)] ≤ 3.0 X
             ULN within 72 hours of initiating the Induction Cycle

          -  Baseline prothrombin time (PT)/international normalized ratio (INR) ratio < 3 X ULN
             within 7 days of initiating the Induction Cycle (for subjects with correctable
             coagulation abnormalities, coagulation factor support per institutional standard of
             care for AML is allowed)

          -  Partial thromboplastin time (PTT) < 3 X ULN within 7 days of initiating the Induction
             Cycle (for subjects with correctable coagulation abnormalities, coagulation factor
             support per institutional standard of care for AML is allowed)

          -  Negative pregnancy test within 14 days prior to study treatment (for Women of
             reproductive potential only)

          -  Women of child-bearing potential and men must agree (in ICF) to use adequate
             contraception (eg, hormonal or barrier methods of birth control; abstinence;
             sterilized partner) for the duration of study participation

          -  Ability to understand and the willingness to sign the written informed consent
             document

        EXCLUSION CRITERIA

          -  Received anticancer therapy (chemotherapy, immunotherapy, radiotherapy, or
             investigational therapy) within 2 weeks prior to starting study treatment [EXCEPTION:
             Hydroxyurea (hydrea) to control high white blood cell count is permitted]

          -  Receiving any other investigational agents within 14 days or 5 effective half lives
             (whichever is shorter) prior to 1st dose of ibrutinib

          -  Prior treatment with ibrutinib

          -  Known unresolved toxicities due to prior anticancer therapy [≥ Grade 2, by Common
             Terminology Criteria for Adverse Events (CTCAE) v4.03] unless otherwise defined in the
             inclusion/exclusion criteria (EXCEPTION: alopecia)

          -  Known acute promyelocytic leukemia (French-American-British Class M3-AML)

          -  Known active central nervous system (CNS) leukemia

          -  Prior bone marrow transplant presenting with active uncontrolled graft vs host disease
             (GvHD)

          -  Known congenital bleeding disorders, such as hemophilia

          -  Known history of stroke or intracranial hemorrhage within 6 months prior to study
             treatment

          -  Concomitant use of warfarin or other vitamin K antagonists

          -  Requires treatment with strong CYP3A inhibitors at the time of study enrollment.
             Washout period is 5 effective half-lives is required prior to 1st dose of ibrutinib

          -  Requires treatment with strong CYP3A inducers at the time of study enrollment. Washout
             period is 5 effective half-lives is required prior to 1st dose of ibrutinib

          -  Known active uncontrolled systemic infection

          -  Major surgery within 4 weeks of 1st dose of ibrutinib

          -  Unable to swallow capsules

          -  Known Malabsorption syndrome

          -  Known Disease significantly affecting gastrointestinal function

          -  Resection of the stomach or small bowel

          -  Uncontrolled symptomatic inflammatory bowel disease

          -  Ulcerative colitis

          -  Bowel obstruction, partial or complete

          -  Congestive heart failure with ejection fraction (EF) < 45%

          -  Uncontrolled cardiac disease, including uncontrolled cardiac arrhythmia or coronary
             artery disease (CAD) with active symptoms due to CAD defined as unstable angina

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to ibrutinib; idarubicin; or cytarabine

          -  Uncontrolled intercurrent illness including, but not limited to:

          -  Active infection

          -  Psychiatric illness/social situations that would limit compliance with study
             requirements

          -  Pregnant

          -  Lactating

          -  Known positive HIV

          -  Known active hepatitis C

          -  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)
      