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)