Participants will be randomized 1:1 to receive either belumosudil or Best Available Therapy (BAT), with stratification based on baseline cGVHD severity as defined by the 2014◦NIH consensus criteria (moderate versus severe), use of concomitant CS and/or CNI (ie, tacrolimus or cyclosporine) at baseline (Yes versus No), and the number of prior lines of therapies (2 versus more than 2). While treatment practices for cGVHD differ across regions, ruxolitinib has been approved by the European Commission since May 2022 and is expected to be broadly accessible throughout most EU member states by study initiation. The study will target patients post-ruxolitinib treatment, except where Investigators deemed ruxolitinib treatment for cGVHD not suitable. In the BAT arm, the study doctor will select one BAT based on clinical judgement, local availability etc. prior to randomization.
Participants randomized to the BAT arm will have the option to cross-over to open-label belumosudil treatment upon meeting predefined criteria.
Study details include:
* The study duration will be defined as 3 years from LPI. * Individual participant duration on study will consist of:
* Up to 28 days for screening. * Treatment until clinically significant progression of cGVHD, relapse/recurrence of the underlying disease, start of a new systemic treatment for cGVHD (except change from BAT to belumosudil during the cross-over), experience of an unacceptable adverse event, request from participant or Investigator, or until the end of the study is reached, whichever comes first. * Thirty days of post treatment safety follow-up. * Follow-up for cGVHD status as applicable. * Long-term follow-up until death or end of study, whichever occurs first.
Participant must be at least 12 years of age at the time of signing the informed consent.
Participants who have undergone allo-HCT.
Participants with active moderate to severe cGVHD at the time of enrollment, defined using the NIH Consensus diagnosis and staging criteria for which the physician believes a new line of systemic therapy is required.
Participant receiving systemic CNI and/or CS must be on a stable dose/regimen (prednisone equivalent <1 mg/kg/day for CS) for at least 2 weeks prior to randomization.
Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of progressive or relapsed underlying disease or post-transplant lymphoproliferative disease after most recent allo-HCT.
Participants who newly initiated any systemic cGVHD treatment within 14 days prior to the date of randomization.
Ruxolitinib must be tapered and discontinued within 14 days following the first dose of belumosudil or BAT (allowing for a maximum overlap period of up to 14 days with belumosudil or BAT treatment).
No dose increases of ruxolitinib are permitted from 14 days prior to the date of randomization until permanent discontinuation of ruxolitinib (dose reductions and discontinuations are permitted during this period).
Parallel
Belumosudil
DrugPharmaceutical form:Tablet-Route of administration:oral
Best available therapy (BAT)
Other interventionParticipants will receive BAT based on the Investigator's judgment
Overall response rate
Overall response rate at 24 weeks defined as the proportion of participants who achieve an overall response (PR or CR) without the requirement of new systemic therapy as per NIH consensus response criteria (2014) at Week 24.
Time from the date of randomization to the date of start of new systemic treatment for cGVHD, relapse or recurrence of underlying disease, or death, whichever occurs first.
Proportion of participants achieving at least 6-point reduction from baseline in the modified Lee cGVHD Symptom Scale score at Week 24.
Proportion of participants who achieve an overall response (CR or PR) within up to 24 weeks and without the requirement of new systemic therapy as per NIH consensus response criteria (2014).
Proportion of participants who achieve an overall response (CR or PR) based on NIH consensus response criteria (2014) at any time until start of new systemic therapy for cGVHD.
This trial is not recruiting at the moment. You can still explore other options:
