Comparing the Therapeutic Effects of Using Ruxolitinib and Steroids Concurrently to Steroids Alone As Initial Treatment in Patients Diagnosed with Chronic Graft-versus-host Disease At a Grade of Moderate or Higher Severity
- Conditions
- GVHD - Graft-Versus-Host DiseaseHaematopoietic Stem Cell TransplantationNeoplasms
- Interventions
- Registration Number
- NCT06756061
- Lead Sponsor
- Byung-Sik Cho
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 88
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Prednisone Prednisone The 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. Prednisone + Jakavi(ruxolitinib) Prednisone + Jakavi(ruxolitinib) The 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.)
- Primary Outcome Measures
Name Time Method Overall Response Rate(ORR) on 48 week 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.
- Secondary Outcome Measures
Name Time Method Ratio of subjects who are found steroid-refractory or steroid-dependent on Weeks 1, 4, 24, 36 and 48 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 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) for 48 weeks 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) for 48 weeks 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.
Ratio of subjects whose daily dosage of systemic corticosteroid is reduced as much as at least 50% compared to the baseline on Week 48 All corticosteroid dosages administered to participants, along with any dose adjustments made during the study, were documented to evaluate participants who achieved a ≥ 50% reduction in their daily corticosteroid dose.
Ratio of subjects whose daily dosage of systemic corticosteroid is reduced compared to the baseline on Week 48 All corticosteroid dosages administered to participants, along with any dose adjustments made during the study, were documented for assessment of participants with any degree of reduction in daily corticosteroid dose.
Time up to the point of stopping systemic immunosuppressant administration (concomitant medicines other than IMPs) for 48 weeks All systemic immunosuppressant dosages administered to participants, along with any dose adjustments during the study, were documented to assess participants who successfully discontinued all systemic immunosuppressants. Participants who were classified as having completely tapered off immunosuppressants were those who permanently ceased their use as recorded in the dose administration records and did not restart treatment within the same interval. Participants who discontinued immunosuppressants and remained in follow-up were also considered tapered off, with a recorded dose of 0 in subsequent intervals unless they restarted immunosuppressant treatment or withdrew from the main treatment period.
Change in FACT-BMT((Functional Assessment of Cancer Therapy - Bone Marrow Transplantation) score compared to the baseline on Week 24, 36 and 48 Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The FACT-BMT is a 50-item self-report questionnaire that measures the effect of a therapy on domains including physical, functional, social/family, and emotional well-being, together with additional concerns relevant for bone marrow transplantation participants. The questions were based on a 5-point Likert scale, where 0 corresponds to "not at all" and 4 corresponds to "very much." The higher the final score, the better the quality of life. The FACT-BMT total score ranges from 0 to 148.
Change in EQ-5D-5L(European Quality of Life 5 Dimension) score compared to the baseline on Week 24, 36 and 48 The EQ-5D-5L is a descriptive classification consisting of five dimensions of health: mobility, self-care, usual activities, anxiety/depression, and pain/discomfort. The five-level version (no problems, slight problems, moderate problems, severe problems, and extreme problems) uses a 5-point Likert scale, with 1 being no problems and 5 being extreme problems.
Trial Locations
- Locations (1)
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Banpo-daero/Seocho-gu, Korea, Republic of