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

Background: * Chronic graft-versus-host disease (GvHD) is the leading cause of late morbidity and non-relapse mortality following allogeneic hematopoietic stem cell transplantation (alloHSCT), occurring in 40-60% long-term survivors. * Chronic GvHD occurs due to the dysfunctional peripheral tolerance during post-transplant hematopoietic reconstitution that allows the development and persistence of alloreactive donor-derived T and B cells. * Prednisone is the front-line therapy; however, about 50% of participants have steroid-refractory disease and there is no standard second-line therapy. * The most attractive approach for controlling chronic GvHD would be early therapy intervention which could prevent the most severe and irreversible clinical manifestations. * Anti-B-cell therapy delivered early in chronic GvHD could be effective and steroid-sparing. * Ibrutinib, reversible small molecule inhibitor of Brutons tyrosine kinase, has been shown to be well-tolerated and effective in phase 1b/2 trial for steroid refractory chronic GvHD. Objective: -To evaluate efficacy of ibrutinib as a first-line treatment for persons with newly diagnosed chronic GvHD by measuring the overall response rate (complete response \[CR\] + partial response \[PR\]) at 6 months, according to the 2014 National Institutes of Health (NIH) Consensus Criteria Eligibility: * Newly diagnosed, moderate or severe chronic GvHD according to the 2014 NIH Consensus Criteria, requiring systemic immunosuppression * Age greater than or equal to 18 years old * Karnofsky performance status greater than or equal to 60% * History of prior alloHSCT; any donors, conditioning regimens and graft sources are allowed * Adequate cardiac, hepatic and other organ function * Adequate laboratory parameters Design: * Multi-center, non-randomized, phase II study * Two-stage design will be used to determine the overall response rate (CR + PR) at 6 months * Continuous daily dose of ibrutinib 420 mg by mouth, with the potential for dose reductions to 280 mg and 140 mg * The accrual ceiling will be set at 40 participants, allowing for a total of up to 28 evaluable subjects.