study of efficacy and safety of ruxolitinib in patients with grade ii to iv steroid-refractory acute graft vs. host disease

Conditions: Steroid-refractory Acute Graft Versus Host Disease

Summary: the purpose of this study is to assess the efficacy and safety of ruxolitinib therapy in chinese adults and adolescents (≥ 12 years old) with grade ii-iv steroid-refractory acute graft versus host disease (sr-agvhd).

participants will start with a screening period to assess the eligibility; only participants who meet all the inclusion and none of the exclusion criteria will start study treatment from day 1 to week 24 or end of treatment. following safety follow up visits, participants will receive the long-term follow-up until month 12.

Eligibility criteria:
key inclusion criteria * male or female chinese participants aged 12 or older at the time of informed consent. written informed consent from participant, parent or legal guardian. * 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. * clinically diagnosed grades ii to iv acute gvhd as per standard criteria occurring after allosct requiring systemic immune suppressive therapy. * evident myeloid and platelet engraftment (confirmed within 48 hours prior to study treatment (ruxolitinib) start): * confirmed diagnosis of steroid refractory agvhd defined as participants administered high-dose systemic corticosteroids (methylprednisolone 2 mg/kg/day \[or equivalent prednisone dose 2.5 mg/kg/day\]), given alone or combined with calcineurin inhibitors (cni) and either: 1. progression based on organ assessment after at least 3 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- cni for the treatment of grade ii to iv agvhd. or 2. failure to achieve at a minimum partial response based on organ assessment after 7 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/-cni for the treatment of grade ii to iv. or 3. participants who fail corticosteroid taper defined as fulfilling either one of the following criteria: * requirement for an increase in the corticosteroid dose to methylprednisolone ≥2 mg/kg/day (or equivalent prednisone dose ≥2.5 mg/kg/day). or * failure to taper the methylprednisolone dose to \< 0.5 mg/kg/day (or equivalent prednisone dose \<0.6 mg/kg/day) for a minimum of 7 days. key exclusion criteria * has received more than one systemic treatment for steroid refractory agvhd. participants who received jak inhibitor therapy for any indication after initiation of current allosct conditioning. * clinical presentation resembling de novo chronic gvhd or gvhd overlap syndrome with both acute and chronic gvhd features. * failed prior allosct within the past 6 months. presence of relapsed primary malignancy after the allosct was performed. * presence of an active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment. * sr-agvhd occurring after non-scheduled donor lymphocyte infusion (dli) administered for pre-emptive treatment of malignancy recurrence. note: participants who have received a scheduled dli as part of their transplant procedure and not for management of malignancy relapse are eligible. * presence of significant respiratory disease, severely impaired renal function, clinically significant or uncontrolled cardiac disease, unresolved cholestatic and liver disorders (not attributable to agvhd). disorders and/or current therapy with medications that interfere with coagulation or platelet function. other protocol-defined inclusion / exclusion criteria may apply

Keywords: sr-agvhd agvhd acute graft-versus-host disease ruxolitinib chinese patients corticosteroid-refractory grade ii-iv grade ii to iv