Phase I/II Study of Pacritinib, A JAK2/IRAK1/CSF1R Inhibitor, in Refractory Chronic Graft-Versus-Host Disease (cGVHD) After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Background: * Chronic GVHD (cGVHD) is a multi-organ disorder characterized by immune dysregulation, impaired organ function, and decreased survival for hematopoietic stem cell transplantation (HSCT) patients. * The JAK-STAT pathway plays an important role in immune cell development and function, including antigen presenting cells, B- and T-cells, and its activation leads to a cascade promoting a proinflammatory cytokine milieu. * Pacritinib is a JAK2/IRAK1/CSF1R/FLT3 inhibitor, with an established safety and efficacy profile in the treatment of myeloproliferative neoplasms (myelofibrosis) and of acute GVHD. * Pacritinib s immunomodulatory effects suggest therapeutic benefit for cGVHD, without abrogating the graft-versus-leukemia effect after HSCT. Objectives: * Phase I: to determine the safety of pacritinib in participants with refractory cGVHD * Phase II: to determine the efficacy of pacritinib in participants with refractory cGVHD Eligibility: * Moderate or severe cGVHD (after allogeneic hematopoietic stem cell transplantation) diagnosed and staged per NIH criteria. * cGVHD that did not respond to at least two prior lines of systemic therapy. * Age \>=18 years. * If participant is taking systemic therapy for cGVHD at the time of enrollment, they must be on stable or tapering doses in the preceding 4 weeks. * Participants must have adequate organ and marrow function. Design: * This Phase I/II study will use a modified 3+3 dose-escalation design, with two planned dose levels of pacritinib, followed by a small efficacy evaluation in a randomized phase II design. * Pacritinib will be given taken orally once or twice daily (based on dose level) on days 1- 28 of a 28-day cycle. * Pacritinib treatment will continue for up to 24 months. cGVHD response will be evaluated at 6 weeks, and 3, 6, 9 and 12 months from the start of pacritinib. If patient continues treatment beyond 12 months, cGVHD will be evaluated at 15, 18, 21 and 24 months (off treatment timepoint) from the start of pacritinib. All participants will be followed through 3 years post-initiation of pacritinib. * The accrual ceiling is set at 50 participants.