a study of ruxolitinib vs best available therapy (bat) in patients with steroid-refractory chronic graft vs. host disease (gvhd) after bone marrow transplantation (reach3)

Conditions: Graft-versus-host Disease (GVHD)

Summary: the purpose of this study is to assess the efficacy of ruxolitinib against best available therapy in participants with steroid-refractory chronic graft-versus-host disease (sr cgvhd).


Eligibility criteria:
inclusion criteria: * have undergone allogeneic stem cell transplantation (allosct) from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood. recipients of non-myeloablative, myeloablative, and reduced intensity conditioning are eligible * evident myeloid and platelet engraftment: absolute neutrophil count (anc) \> 1000/mm\^3 and platelet count \> 25,000/ mm\^3 * participants with clinically diagnosed moderate to severe cgvhd according to nih consensus criteria prior to randomization: * moderate cgvhd: at least one organ (not lung) with a score of 2, 3 or more organs involved with a score of 1 in each organ, or lung score of 1 * severe cgvhd: at least 1 organ with a score of 3, or lung score of 2 or 3 * participants currently receiving systemic or topical corticosteroids for the treatment of cgvhd for a duration of \< 12 months prior to cycle 1 day 1 (if applicable), and have a confirmed diagnosis of steroid-refractory cgvhd defined per 2014 nih consensus criteria irrespective of the concomitant use of a calcineurin inhibitor (cni), as follows: * a lack of response or disease progression after administration of minimum prednisone 1 mg/kg/day for at least 1 week, or * disease persistence without improvement despite continued treatment with prednisone at \> 0.5 mg/kg/day or 1 mg/kg/every other day for at least 4 weeks, or * increase to prednisolone dose to \> 0.25 mg/kg/day after 2 unsuccessful attempts to taper the dose * participant must accept to be treated with only one of the following bat options on cycle 1 day 1 (additions and changes are allowed during the course of the study, but only with bat from the following bat options): extracorporeal photopheresis (ecp), low-dose methotrexate (mtx), mycophenolate mofetil (mmf), mtor inhibitors (everolimus or sirolimus), infliximab, rituximab, pentostatin, imatinib, ibrutinib exclusion criteria: * participants who have received 2 or more systemic treatment for cgvhd in addition to corticosteroids ± cni for cgvhd * patients that transition from active agvhd to cgvhd without tapering off corticosteroids ± cni and any systemic treatment \* patients receiving up to 30 mg by mouth once a day of hydrocortisone (i.e., physiologic replacement dose) of corticosteroids are allowed. * participants who were treated with prior jak inhibitors for agvhd; except when the participant achieved complete or partial response and has been off jak inhibitor treatment for at least 8 weeks prior to cycle 1 day 1 * failed prior allosct within the past 6 months from cycle 1 day 1 * participants with relapsed primary malignancy, or who have been treated for relapse after the allosct was performed * steroid refractory cgvhd occurring after a non-scheduled donor lymphocyte infusion (dli) administered for preemptive treatment of malignancy recurrence. participants who have received a scheduled dli as part of their transplant procedure and not for management of malignancy relapse are eligible * any corticosteroid therapy for indications other than cgvhd at doses \> 1 mg/kg/day methylprednisolone or equivalent within 7 days of cycle 1 day 1

Keywords: graft-versus-host disease (gvhd) chronic gvhd (cgvhd) steroid-refractory ruxolitinib janus kinase inhibitor