Ibrutinib in Treating Patients With Advanced Systemic Mastocytosis

INCLUSION CRITERIA * Diagnosis of systemic mastocytosis per 2008 World Health Organization (WHO) criteria. Those with advanced systemic mastocytosis (ASM); mast cell leukemia (MCL); or systemic mastocytosis-associated hematological clonal non-mast cell lineage disease (SM-AHNMD) required to have at least 1 organ damage finding * Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN); if considered related to ASM/MCL ≤ 5 x ULN * Estimated creatinine clearance ≥ 30 mL/min (Cockcroft-Gault) * Total bilirubin ≤ 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin); if considered related to ASM/MCL ≤ 3 x ULN * Female subjects must be of non-reproductive potential, or if of childbearing potential must have a negative serum pregnancy test upon study entry * Must agree to use highly effective methods of birth control * Written informed consent * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3 * Life expectancy \> 12 weeks EXCLUSION CRITERIA * Received any investigational agent, chemotherapy, interferon-alpha, or 2-chlorodeoxyadenosine (2-CdA, cladribine) within 30 days prior to day 1; or monoclonal antibody ≤ 6 weeks prior to first administration of study treatment (patients with an AHNMD with progressive leukocytosis who require control of their counts are permitted to receive hydroxyurea) * Diagnosis of AHNMD requiring immediate cytoreductive therapy or targeted drugs (eg, acute myeloid leukemia \[AML\]) * 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 at low risk for recurrence * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease * Adequately treated carcinoma in situ without evidence of disease * Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc., or chronic administration \[\> 14 days\] of \> 10 mg/day of prednisone) within 28 days of the first dose of study drug * Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug * Systemic treatment for infection completed ≤ 14 days before the first dose of study drug * Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4), grade 0 or 1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia * Known bleeding disorders (eg, severe von Willebrand's disease) or severe hemophilia * History of stroke or intracranial hemorrhage within 6 months prior to enrollment * Known history of human immunodeficiency virus (HIV) or * Active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) * Major surgery within 4 weeks of first dose of study drug * Any life-threatening illness, medical condition, or organ system dysfunction that 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 * Resection of the stomach or small bowel * Symptomatic inflammatory bowel disease * Ulcerative colitis * Partial or complete bowel obstruction * Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor * 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) * Known hypersensitivity to any excipient contained in the drug * Received hematopoietic growth factor support within 14 days of day 1 of ibrutinib (Jehovah's witnesses may be given an erythropoiesis-stimulating agent before and during the trial in lieu of red blood cell transfusions but anemia and/or red blood cell (RBC) transfusion dependence cannot be used for response assessment in these patients) * Presence of the factor interacting with poly(A) polymerase alpha (PAPOLA) and cleavage and polyadenylation specific factor 1 (CPSF1) (FIP1L1)-platelet-derived growth factor receptor, alpha polypeptide (PDGFRalpha) fusion even with resistance to imatinib (such patients are no longer defined as systemic mastocytosis by the WHO) * Received any treatment with ibrutinib prior to study entry * The concomitant use of warfarin or other vitamin K antagonists unless felt to be of significant clinical need; low molecular weight heparin or other anticoagulants may be used instead if anticoagulation is required