Ibrutinib in Preventing Acute Leukemia in Patients After Reduced-Intensity Conditioning and Stem Cell Transplant

Inclusion Criteria:

* INCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT)
* Diagnosis of acute myeloid leukemia (AML), acute biphenotypic leukemia, or acute lymphoblastic leukemia (ALL); CML transformed to blast crisis is eligible
* Planned allogeneic HCT using fludarabine phosphate (FLU)/melphalan hydrochloride (MEL) or FLU/busulfan (BU) conditioning
* Planned graft versus host disease (GVHD) prophylaxis consisting of tacrolimus (TAC)/methotrexate (MTX) or TAC/sirolimus (SRL)
* Human leukocyte antigen (HLA) identical sibling donor, HLA matched unrelated donor, or donor mismatched at 1 HLA allele or antigen
* Less than or equal to 5% blasts on bone marrow examination within 60 days of starting conditioning
* Age \>= 18 years and =\< 70 years
* Able to give informed consent
* Subjects will be eligible if their planned conditioning regimen for allogeneic HCT consists of one of the two following standard reduced intensity conditioning regimens:

  * FLU/MEL: fludarabine phosphate (fludarabine) 120 to 180 mg/m\^2; melphalan hydrochloride (melphalan) =\< 150 mg/m\^2
  * FLU/BU: fludarabine 120 to 180 mg/m\^2; busulfan =\< 8 mg/kg orally or =\< 6.4 mg/kg intravenously
* Subjects will be eligible if their planned post grafting immunosuppression consists of one of the two following regimens:

  * TAC/MTX: tacrolimus (oral or intravenous) and intravenous methotrexate administered according to institutional standard practice.
  * TAC/SRL: tacrolimus (oral or intravenous) and oral sirolimus, administered according to institutional standards of care
* INCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION)
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
* Absolute neutrophil count (ANC) \> 0.75 x 10\^9/L
* Platelet count \> 50 x 10\^9/L
* Hemoglobin \> 8.0 g/dL without transfusion or growth factor support for at least 7 days prior to screening (with the exception of pegylated granulocyte-colony stimulating factor \[G-CSF\] and darbopoietin, which require at least 14 days of abstinence prior to screening)
* Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3.0 x upper limit of normal
* Estimated creatinine clearance \>= 30 mL/min via Cockroft-Gault formula
* Bilirubin =\< 1.5 x upper limit of normal (unless elevated bilirubin is due to Gilbert's syndrome or of non-hepatic origin)
* Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) (activated partial thromboplastin time \[aPTT\]) =\< 1.5 x upper limit of normal
* Female subjects who are of non-reproductive potential (ie, post-menopausal by history - no menses for \>= 1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy); female subjects of childbearing potential must have a negative serum pregnancy test upon screening
* Male and female subjects who agree to use both a highly effective method of birth control (eg, implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], sexual abstinence, or sterilized partner) and a barrier method (eg, condoms, vaginal ring, sponge, etc) during the period of therapy and for 30 days after the last dose of study drug for females and 90 days after the last dose of the study drug for males
* Between day +60 and day +90 after allogeneic HCT

Exclusion Criteria:

* EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Active involvement of the central nervous system with malignancy (previous central nervous system \[CNS\] involvement is allowed if clearance of CNS disease has been documented prior to enrollment)
* EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Pregnant or breastfeeding
* EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Karnofsky performance status \< 60%
* EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Active leukemia (\> 5% leukemic blasts in peripheral blood or bone marrow)
* EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Non-hematologic malignancy with a life expectancy of \< 5 years
* EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection; subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment; those who are PCR positive will be excluded
* EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Known bleeding disorders (eg, von Willebrand's disease) or hemophilia
* EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): 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 felt to be at low risk for recurrence by treating physician
  * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Active and uncontrolled acute GVHD grades III or IV
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Use of secondary therapy for acute GVHD at any time (defined as any systemic therapy intended to treat acute GVHD besides corticosteroids)
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Requirement for anticoagulation with warfarin or other vitamin K antagonists (concomitant use of other anticoagulants is permitted)
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Relapsed leukemia (\> 5% leukemic blasts in peripheral blood or bone marrow after allogeneic HCT)
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Karnofsky performance status \< 60%
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Chemotherapy =\< 21 days prior to first administration of study treatment and/or monoclonal antibody =\< 6 weeks prior to first administration of study treatment
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): 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
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): History of stroke or intracranial hemorrhage within 6 months prior to screening
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Any life threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Major surgery within 4 weeks of first dose of study drug
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Any uncontrolled active systemic infection
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Unresolved toxicities from prior anti cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4), grade =\< 1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Unwilling or unable to participate in all required study evaluations and procedures
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): 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)
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Currently active, clinically significant hepatic impairment (Child-Pugh class B or C)
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Lactating or pregnant
* EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Uncontrolled cardiac arrhythmias