Front Line Ibrutinib Without Corticosteroids for Newly Diagnosed Chronic Graft-versus-Host Disease

* INCLUSION CRITERIA: 1. Newly diagnosed moderate or severe chronic Graft versus Host Disease (GvHD) (according to the 2014 National Institutes of Health (NIH) Consensus Criteria, requiring systemic immunosuppression. 2. History of prior allogeneic Hematopoietic Stem Cell Transplant (HSCT) (any donors, conditioning regimens and graft sources are allowed). 3. Subjects may have ongoing acute GvHD features (e.g., erythematous rash, elevated liver enzymes, diarrhea) which are in the opinion of the investigator responding to therapy. 4. Stable doses of other immunosuppressive medications (e.g., calcineurin inhibitors, mycophenolate mofetil, rapamune, etc.) with no dose increase in the 2 weeks prior to study treatment initiation. Doses may be adjusted for trough levels. 5. Age greater than or equal to 18 years old. 6. Karnofsky performance status greater than or equal to 60%. 7. Laboratory parameters as defined below: * Serum creatinine less than or equal to 2.0 x upper limit of normal (ULN). * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x ULN (less than or equal to 5 x ULN if unequivocal liver GvHD). * Total bilirubin less than or equal to 3 x ULN. * Absolute neutrophil count greater than or equal to 1.0 x 10(9)/L (no growth factor support allowed). * Platelets \> 50 x 10(9)/L (no transfusions allowed less than or equal to 7 days prior to enrollment). 8. Ability to understand and willingness to sign a written informed consent form. 9. The effects of ibrutinib on the developing fetus are unknown. For this reason and because tyrosine kinase inhibitors may be teratogenic, female subjects of childbearing potential and men must agree to use highly effective methods of birth control (hormonal or barrier method of birth control; abstinence) prior to study entry, during the period of therapy, and for 30 days after the last dose of study drug. EXCLUSION CRITERIA: 1. Relapsed or progressive malignant disease (other than minimal residual disease). 2. History of other malignant diseases, including post-transplant lymphoproliferative disease, with the following exceptions: * Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to prior to study treatment initiation and felt to be at low risk for recurrence. * Adequately treated non-melanomatous skin cancer or lentigo malignant melanoma without current evidence of disease. * Adequately treated cervical carcinoma in situ without current evidence of disease. 3. Received previous systemic treatment for chronic GvHD other than less than or equal to 0.5 mg/kg/day of prednisone equivalent for more than 7 days. Subject may be on steroids that were used to treat acute GvHD and then developed chronic GvHD before completing a taper. At the time of enrollment, the dose should be less than or equal to 0.5 mg/kg/day of prednisone equivalent with no dose increase in the preceding 2 weeks before study treatment initiation. 4. Prior or current treatment with: * Ibrutinib since the time of transplant (participants may have received ibrutinib prior to transplant for indications other than chronic GvHD). * Extracorporeal photopheresis (ECP) for acute GvHD less than or equal to 2 weeks prior to study treatment initiation; including any treatment with ECP for chronic GvHD. * Rituximab or other anti-B cell specific antibodies less than or equal to 4 weeks prior to study treatment initiation. * Any systemic investigational agents less than or equal to 4 weeks prior to study treatment initiation. 5. Impaired cardiac function including any one of the following: * Myocardial infarction, unstable angina or acute coronary syndrome less than or equal to 6 months prior to study treatment initiation. * Class 3 or 4 congestive heart failure, uncontrolled arrhythmia or uncontrolled hypertension at any time. 6. Uncontrolled infections (including prior aspergillosis) not responsive to antibiotics, antiviral medicines, or antifungal medicines. 7. Known bleeding disorder or subjects who received a strong cytochrome P450 (CYP) 3A inhibitor less than or equal to 7 days prior to the first dose of ibrutinib or requirement for continuous treatment with a strong CYP3A inhibitor. 8. Active hepatitis C virus (HCV) or hepatitis B virus (HBV). Subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result to be enrolled. 9. Known hypersensitivity to ibrutinib. 10. Pregnant women are excluded from this study because ibrutinib has potential for teratogenic and abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ibrutinib, breastfeeding should be discontinued if the mother is treated with ibrutinib. Women who are planning to become pregnant and men who plan to father a child while enrolled in this study or less than or equal to 30 days after the last dose of study drug are excluded. 11. Any other reason at the discretion of the investigators and documented in the medical record that may raise concerns about the subject safety or ability to participate on this study. 12. Currently active, severe hepatic impairment Child-Pugh class C according to the Child Pugh classification.