A Nation-wide, Multi-center, Prospective, Randomized, Parallel-group, Open-label, Investigator Initiated Pilot Study to Evaluate Efficacy and Safety of Systemic Corticosteroid Plus Ruxolitinib as First-line Therapy in Patients With New-onset Moderate to Severe Chronic Graft-versus-host Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 88
- 试验地点
- 1
- 主要终点
- Overall Response Rate(ORR)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
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.)
干预措施: Prednisone + Jakavi(ruxolitinib) (Drug)
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.
干预措施: Prednisone (Drug)
结局指标
主要结局
Overall Response Rate(ORR)
时间窗: 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.
次要结局
- Ratio of subjects who are found steroid-refractory or steroid-dependent(on Weeks 1, 4, 24, 36 and 48)
- Overall Response Rate (ORR) based on the NIH Consensus Criteria on Weeks 24 and 36(on Weeks 24 and 36)
- Failure-free Survival (FFS)(for 48 weeks)
- Duration of Response (DOR)(for 48 weeks)
- Ratio of subjects whose daily dosage of systemic corticosteroid is reduced as much as at least 50%(compared to the baseline on Week 48)
- Ratio of subjects whose daily dosage of systemic corticosteroid is reduced(compared to the baseline on Week 48)
- Time up to the point of stopping systemic immunosuppressant administration (concomitant medicines other than IMPs)(for 48 weeks)
- Change in FACT-BMT((Functional Assessment of Cancer Therapy - Bone Marrow Transplantation) score(compared to the baseline on Week 24, 36 and 48)
- Change in EQ-5D-5L(European Quality of Life 5 Dimension) score(compared to the baseline on Week 24, 36 and 48)
研究者
Byung-Sik Cho
professor
Seoul St. Mary's Hospital