Chronic graft-versus-host disease (cGVHD) is a complication that occurs in 30-40% of recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is a major cause of late non-relapse mortality. In cases where the initial treatment response is inadequate, irreversible tissue damage often persists, making it a fatal complication that significantly reduces quality of life even for long-term survivors.
Therefore, the success of first-line treatment is crucial, but to date, there are no approved drugs specifically for the first-line treatment of chronic graft-versus-host disease. Besides corticosteroids, which have been used palliatively for over 50 years, there are no proven effective treatments available.
Against this background, this study was designed to explore the potential of new treatments as first-line therapy for chronic graft-versus-host disease, where effective treatment options are currently lacking.
Initially, the objective response rate will be analyzed at the 48-week mark based on the NIH Consensus Criteria (Lee 2015). Additionally, the study will evaluate the proportion of patients with steroid-resistant or steroid-dependent conditions, the objective response rate(ORR), failure-free survival(FFS), duration of response(DOR), and the proportion of patients who have reduced corticosteroids. Furthermore, the differences in treatment effects between the two groups of patients will be analyzed based on safety endpoints, including adverse events, laboratory tests, physical examinations, and vital signs.
Adult men and women aged 19 or older based on the date of signing on the informed consent form
On the screening visit, those who are diagnosed of a moderate to severe chronic graft-versus-host disease according to 2014 NIH consensus criteria
At least 2 points for the lungs
Those who have no history of systemic treatment for chronic graft-versus-host disease and now need systemic corticosteroid treatment
None
Parallel
Prednisone + Jakavi(ruxolitinib)
DrugThe experimental group will receive ruxolitinib 10 mg orally twice daily (BID) and prednisone (or equivalent) at a dosage of 1 mg/kg/day. Subjects are orally administered with an investigational medicinal product (IMP) according to their designated treatment group for 48 weeks, and the investigator may adjust the dosage of IMPs based on symptoms of the target disease. (However, after the 48-week mark, participants in the ruxolitinib treatment group may continue to receive ruxolitinib for an additional maximum of 2 years, based on the investigator's judgment regarding the need for ongoing treatment. The total duration of ruxolitinib administration will not exceed 3 years.)
Prednisone
DrugThe control group will receive prednisone (or equivalent) at a dosage of 1 mg/kg/day. Subjects are orally administered with an investigational medicinal product (IMP) according to their designated treatment group for 48 weeks, and the investigator may adjust the dosage of IMPs based on symptoms of the target disease.
Overall Response Rate(ORR)
ORR was defined as the proportion of participants in each study arm achieving either a complete response (CR) or partial response (PR) based on chronic GvHD (cGvHD) assessments in accordance with the National Institutes of Health Consensus Criteria. Response scoring was compared against the organ score at the time of randomization. CR was characterized by the complete resolution of all cGvHD-related signs and symptoms across all evaluable organs, without the initiation or addition of new systemic therapies. PR was defined as improvement in at least one organ (e.g., an increase of 1 or more points on a 4- to 7-point scale, or an increase of 2 or more points on a 10- to 12-point scale) with no progression in other organs or sites and without the need for initiation or addition of new systemic therapies. Participants requiring additional systemic therapies for earlier progression, mixed response, or non-response were classified as not achieving response.
Ratio of subjects who are found steroid-refractory or steroid-dependent
All corticosteroid dosages administered to participants, along with any dose adjustments made during the study, were documented to evaluate participants meeting specific criteria.Steroid-refractory chronic GvHD(SR-cGVHD) was defined as either progression of cGVHD while receiving prednisone at a dose of ≥1mg/kg/day for at least 1 week or stable cGVHD while on≥0.5mg/kg/day or ≥1mg/kg every other day(EOD) for at least 1 month.Response criteria were based on the National Institutes of Health Consensus Criteria.Progression was defined as worsening in any organ or site or the need to initiate or add new systemic therapies.Participants who did not meet the criteria for overall response or progression were categorized as stable.Steroid-dependent participants were defined as those for whom at least two corticosteroid tapering attempts, spaced at least 8 weeks apart, had failed, requiring corticosteroid doses\>0.25 mg/kg/day or \>0.5mg/kg/day EOD to prevent recurrence or progression of symptoms.
Overall Response Rate (ORR) based on the NIH Consensus Criteria on Weeks 24 and 36
ORR was defined as the proportion of participants in each study arm achieving either a complete response (CR) or partial response (PR) based on chronic GvHD (cGvHD) assessments in accordance with the National Institutes of Health Consensus Criteria. Response scoring was compared against the organ score at the time of randomization. CR was characterized by the complete resolution of all cGvHD-related signs and symptoms across all evaluable organs, without the initiation or addition of new systemic therapies. PR was defined as improvement in at least one organ (e.g., an increase of 1 or more points on a 4- to 7-point scale, or an increase of 2 or more points on a 10- to 12-point scale) with no progression in other organs or sites and without the need for initiation or addition of new systemic therapies. Participants requiring additional systemic therapies for earlier progression, mixed response, or non-response were classified as not achieving response.
Failure-free Survival (FFS)
Composite time to event endpoint incorporating the following FFS events: (i) relapse or recurrence of underlying disease or death due to underlying disease, (ii) nonrelapse mortality, or (iii) addition or initiation of another systemic therapy for cGvHD.
Duration of Response (DOR)
DOR was defined as the time from first response until cGvHD progression, death, or the date of change/addition of systemic therapies for cGvHD and as assessed for responders only. Response was based on cGvHD disease assessments (National Institutes of Health consensus criteria). Duration of response was evaluated in participants who achieved a CR or PR at or before Cycle 7 Day 1.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
Adverse events (AEs) were defined as the onset or worsening of any undesirable signs, symptoms, or medical conditions that occurred after the participant provided signed informed consent. Abnormal laboratory values or test results following informed consent were classified as AEs only if they resulted in clinical signs or symptoms, were deemed clinically significant, required intervention (e.g., treatment for hematologic abnormalities such as transfusion or hematopoietic stem cell support), or necessitated changes in study medication(s). Treatment-emergent adverse events (TEAEs) were defined as AEs that began or worsened during the on-treatment period, which included both the randomized and cross-over phases of the study.
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