Ibrutinib, Idarubicin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

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)