study of efficacy and safety of ruxolitinib in chinese participants with corticosteroid-refractory chronic graft vs. host disease

Conditions: Graft vs. Host Disease; Chronic Graft vs. Host Disease; Corticosteroid-refractory Chronic Graft vs. Host Disease

Summary: the purpose of the study is to assess the efficacy and safety of ruxolitinib in chinese adult and pediatric participants aged 12 years or older with corticosteroid-refractory chronic graft vs. host disease (sr-cgvhd).

this is a single arm, multi-center, open label study which will enroll approximately 50 participants and investigate the efficacy and safety of ruxolitinib administered in adult and adolescent (≥12 years old) chinese participants with sr-cgvhd. the total duration on study for an individual participant will be up to 164 weeks (approximately 3 years). the study consists of following periods, with each cycle comprised of 4 weeks (28 days): * screening period (day -28 to day -1) * treatment period (day 1 to cycle 39/eot) * safety follow-up (last dose +30 days) * long-term survival follow-up period (eot to 156 weeks on study).

Eligibility criteria:
inclusion criteria: * signed informed consent must be obtained prior to participation in the study. * male or female chinese participants aged 12 or older at the time of informed consent * able to swallow tablets.- have undergone 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) \>1,000/mm3 and * platelet count ≥25,000/mm3 note: use of growth factor supplementation and transfusion support is allowed during the trial, however, transfusion to reach a minimum platelet count for inclusion is not allowed during screening and at baseline. * participants with clinically diagnosed cgvhd staging of moderate to severe according to nih consensus criteria (jagasia et al 2015) prior to cycle 1 day 1. * 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 corticosteroids for the treatment of cgvhd for a duration of \< 12 months prior to cycle 1 day 1, and have a confirmed diagnosis of corticosteroid refractory cgvhd defined per 2014 nih consensus criteria (martin et al 2015) irrespective of the concomitant use of a calcineurin inhibitor, as follows: * a lack of response or disease progression after administration of minimum prednisone 1 mg/kg/day for at least 1 week (or equivalent) 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 equivalent) or * increase to prednisone dose to \>0.25 mg/kg/day after two unsuccessful attempts to taper the dose (or equivalent) * participants has eastern cooperative oncology group (ecog) performance status of 0-2 exclusion criteria: for a full list of exclusion criteria, refer to section 5.2. key exclusion criteria include * participants who have received two or more systemic treatments for cgvhd in addition to corticosteroids ± cni for cgvhd. * participants who have received rock2 inhibitors for cgvhd. * participants that transition from active agvhd to cgvhd without tapering off corticosteroids ± cni and any systemic treatment note: participants 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. * sr-cgvhd occurring after a non-scheduled donor lymphocyte infusion (dli) administered for pre-emptive 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. other protocol-defined inclusion/exclusion may apply.

Keywords: cgvhd gvhd sr-cgvhd ruxolitinib inc424 chinese adult pediatric corticosteroid refractory