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

Inclusion Criteria

• Patients must have a previous morphologically confirmed diagnosis of AML based on World Health Organization (WHO) criteria
• Patients must have received at least one prior chemotherapy regimen for their AML and they may have received any type of chemotherapy; disease relapse or the presence of refractory disease must be documented by bone marrow examination demonstrating > 5% blasts in the bone marrow not attributable to another cause; administration of hydrea to control high white blood cell (WBC) count is permitted
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Life expectancy of greater than 4 weeks
• Patients must have platelet count >= 10,000/mm^3 within 72 hours of initiating the induction cycle (for patients with platelets < 10,000/mm^3 at baseline, platelet transfusion support is allowed which is institutional standard of care for AML)
• Patients must have a serum creatinine =< 2.0 mg/dL within 72 hours of initiating the induction cycle
• Patients must have a total bilirubin =< 2.1 mg/dL within 72 hours of initiating the induction cycle, unless the elevation is due primarily to elevated unconjugated hyperbilirubinemia secondary to Gilbert’s syndrome or hemolysis or non-hepatic origin, and not to liver dysfunction
• Patients must have serum glutamic oxaloacetic transaminase (SGOT) aspartate aminotransferase (AST) =< 3.0 x institutional upper limit of normal and serum glutamate pyruvate transaminase (SGPT) alanine aminotransferase (ALT) =< 3.0 x institutional upper limit of normal within 72 hours of initiating the induction cycle
• Patients must have baseline prothrombin time (PT)/international normalized ratio (INR) < 3 x institutional upper limit of normal and partial thromboplastin time (PTT) < 3 x ULN within 7 days of initiating the induction cycle; (for patients with coagulation abnormalities that are correctable, coagulation factor support per institutional standard of care for AML is allowed)
• Women of reproductive potential must have a negative pregnancy test within 14 days prior to study treatment; women who are pregnant are ineligible for this study; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study treatment, for the duration of study participation, and 30 days after completion of ibrutinib administration; women of child-bearing potential and men must agree to use adequate contraception (eg, hormonal or barrier methods of birth control; abstinence; sterilized partner) for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Patients who have had anticancer therapy (chemotherapy, immunotherapy, radiotherapy, or investigational therapy) within 2 weeks prior to starting study treatment; hydroxyurea is an exception; administration of hydrea to control high WBC is permitted
• Patients who are receiving any other investigational agents within 14 days or 5 effective half-lives (whichever is shorter) prior to first (1st) dose of ibrutinib
• Prior treatment with ibrutinib
• Known unresolved toxicities due to prior anticancer therapy, defined as not having resolved to grade 0 or 1 (by Common Terminology Criteria for Adverse Events [CTCAE] version 4 criteria), unless otherwise defined in the inclusion/exclusion criteria with the exception of alopecia
• Patients with known acute promyelocytic leukemia (French-American-British class M3-AML)
• Patients with known active central nervous system (CNS) leukemia
• Prior bone marrow transplant presenting with active uncontrolled graft versus (vs.) host disease (GVHD)
• Known congenital bleeding disorders such as hemophilia
• Patients with a history of known stroke or intracranial hemorrhage within 6 months prior to study treatment are excluded
• Concomitant use of warfarin or other vitamin K antagonists (for patients who are discontinuing warfarin or other vitamin K antagonists, a wash-out period of 5 effective half-lives is required prior to 1st dose of ibrutinib)
• Patients who require treatment with strong CYP3A inhibitors at the time of study enrollment; for patients who can safely discontinue prior strong CYP3A inhibitor, a wash-out period of 5 effective half-lives is required prior to 1st dose of ibrutinib; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• Patients who require strong CYP3A inducers at the time of study enrollment are excluded; for patients who can safely discontinue prior strong CYP3A inducers, a wash-out period of 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 study drug
• Unable to swallow capsules or known malabsorption syndrome, known disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, uncontrolled symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction, at the time of study entry
• Patients with congestive heart failure with ejection fraction (EF) < 45% or uncontrolled cardiac disease (such as uncontrolled cardiac arrhythmia, uncontrolled coronary artery disease [CAD] with active symptoms due to CAD defined as unstable angina) are excluded from initiation of study treatment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib or idarubicin or cytarabine
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled active infection, or psychiatric illness/social situations that would limit compliance with study requirements
• Lactating or pregnant; pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ibrutinib
• Patients with known positive human immunodeficiency virus (HIV) are excluded
• Patients with known active hepatitis C are excluded
• 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)