Inclusion Criteria:

• 50 to 110 days post-transplant at time of registration.
• Age ≥ 18 years old.
• HLA matched-related, matched unrelated donors (defined as 8/8 (Class I: HLA A, B, C, and Class II: DRB1)), or HLA-mismatched-unrelated donors (defined as 7/8 (with single mismatch at Class I: HLA A, B, C, or Class II: DRB1)) 
• Karnofsky Performance Status (PS) ≥ 70. 
• The following laboratory values obtained ≤ 7 days prior to registration:  
  • Hemoglobin ≥ 8.0 g/dL (*Untransfused);
  • Absolute neutrophil count (ANC) ≥ 1000/mm^3 *without growth factor support; 
  • Platelet count ≥ 50,000/mm^3 (*Untransfused);
  • PT/INR/aPTT ≤ 1.5 x ULN;
  • Total bilirubin ≤ 1.5 x ULN (unless it is due to Gilbert’s syndrome or causes other than liver); Or  
  • Alanine aminotransferase (ALT) and Aspartate transaminase (AST) ≤ 2 x ULN (unless it is due to Gilbert’s syndrome or causes other than liver).
  • Calculated creatinine clearance ≥ 40 ml/min using the Cockcroft-Gault formula below: 
    • Cockcroft-Gault Equation: 
    • Creatinine clearance for males =    (140 - age)(weight in kg) 
    •                                                           (72)(serum creatinine in mg/dL) 
    • Creatinine clearance for females = (140 - age)(weight in kg)(0.85) 
    •                                                           (72)(serum creatinine in mg/dL) 
• Adequate cardiac and pulmonary function at baseline (may be based on pre-transplant vital organ work up): 
  • Cardiac evaluation to determine left ventricular ejection fraction (LV-EF) if there is any clinical reason (for example an ischemic event or hypovolemic shock) to suspect that the LV-EF was affected from the time of the prior measurement of baseline (required  ≥ 45%);
  • Pulmonary evaluation to determine adequate pulmonary function with a DLCO ≥ 50% predicted value, FEV1 ≥ 50% predicted value and FVC ≥ 50% predicted value.
• Female subjects of childbearing potential must have negative serum pregnancy test ≤ 7 days prior to registration. Female subjects of non-reproductive potential are defined as follows: post-menopausal by history - no menses for ≥1 year; or s/p hysterectomy; or s/p bilateral tubal ligation; or history of bilateral oophorectomy.  
• Male and female subjects agreeable to using both a highly effective method of birth control (for example, implants, injectables, combined oral contraceptives, intrauterine devices [IUDs], or sterilized partner) and a barrier method (e.g., condoms, vaginal ring, sponge, etc.) during the period of therapy and for 90 days after the last dose of study drug. 
• Provide written informed consent. 
• Willingness to provide mandatory blood specimens for correlative research.  
• Willingness to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).  
  • Note: During the Active Monitoring Phase of a study (i.e., active treatment and clinical follow-up), participants must be willing to return to the consenting institution for follow-up.

Exclusion Criteria:

• Uncontrolled acute GVHD at time of registration.
  • Note: Uncontrolled is defined as unable to tolerate tapering down of steroids or other therapies or requiring additional therapies or increase in doses of prescribed therapies.
• Evidence of NIH chronic GVHD preceding registration or at time of registration.
• Relapsed/progressive disease compared to prior to transplant and prior to registration. In this case, baseline represents the baseline disease staging (if no other disease staging has been performed prior to enrollment); or a post-transplant disease staging if that represents the most immediate staging prior to enrollment. In the event that both had been performed, the latest one performed (i.e., the one closest in time to the enrollment to this trial) will be considered the baseline for comparison. 
  • Note: Relapse and progression definitions for each hematologic malignancy/ disorder will follow standard definition.
• Uncontrolled active systemic fungal, viral, bacterial, or other infection.
  • Note: Infections are considered controlled if appropriate therapy has been instituted and at the time of registration have no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection.
• Unable to swallow capsules or impairment/disease significantly affecting gastrointestinal function that may significantly alter the absorption of the drugs (e.g., gastric bypass surgeries, Celiac or Whipple disease).
• Any of the following because this study involves) an agent that has known genotoxic, mutagenic and teratogenic effects:
  • Pregnant persons;
  • Nursing persons;
  • Persons of childbearing potential who are unwilling to employ adequate contraception.
• History of stroke or intracranial hemorrhage ≤ 6 months prior to first dose.
• Active involvement of the central nervous system with malignancy.
  • Note: Previous CNS involvement is allowed if clearance of CNS disease has been documented prior to registration.
• Require anticoagulation with warfarin or other Vitamin K antagonists.
• Any of the following prior therapies:
  • Administration of anti-thymocyte globulin (or equivalent), alemtuzumab, or post transplant cyclophosphamide as part of the conditioning regimen or ≤ 1 month of allograft;
  • Administration of a strong cytochrome P450 (CYP) 3A inhibitor ≤ 7 days prior to the first dose or subjects who require continuous treatment with a strong CYP3A inhibitor.
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Patients known to have tested positive on HIV antibody test.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Chronic liver disease with hepatic impairment Child Pugh class B or C).
• Active hepatitis B or C infection. ​​​​​​​
  • Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. HBcIgM Ab, HBsAg and HCV Ab Scrn w/Reflex testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV infection.
• Receiving any chemotherapy, anticancer immunotherapy, experimental therapy, or radiotherapy is prohibited while the subject is receiving study treatment with ibrutinib. The Sponsor-investigator must be notified in advance (or as soon as possible thereafter) of any instances in which prohibited therapies are administered.
  • EXCEPTIONS: Patients will be allowed to receive antimicrobial prophylaxis appropriate for allogeneic HCT recipients, according to institutional SOP or common clinical practice.
• Other active malignancy ≤ 5 years prior to registration.
  • EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix.
  • Note: If there is a history of prior malignancy, they must not be receiving other treatment for their cancer.
• History of myocardial infarction ≤ 6 months, or uncontrolled cardiac arrhythmias.