Ruxolitinib for Newly Diagnosed Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- absolute FEV1 increase
研究概览
简要总结
Lung is one of the target organs in chronic graft versus host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Bronchiolitis obliterans syndrome (BOS) after allo-HSCT was a clinical syndrome characterized by persistent airflow restriction which is the result of lung cGVHD. BOS is one of the main causes of late mortality after allo-HSCT, severely restricting the daily activities and respiratory function of patients. It limits the quality of life and increased the non-relapse mortality (NRM) after allo-HSCT. Currently, the first-line treatment for BOS is FAM ( oral fluticasone, azithromycin and montelukast). However, more than 50% of patients develop as steroids resistant (SR)-BOS, and SR-BOS has a poor prognosis and irreversible impaired lung function. Ruxolitinib is an effective drug in the treatment of SR-cGVHD. This is a phase Ⅱ prospective clinical study to explore the efficacy and safety of ruxolitinib as a first-line treatment for newly diagnosed BOS after allo-HSCT.
详细描述
The incidence of chronic graft versus host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was 30%-70%, Which extremely limited the quality of life and the survival of patients after allo-HSCT. Lung is one of the target organs in cGVHD after allo-HSCT. Bronchiolitis obliterans syndrome (BOS) after allo-HSCT was a clinical syndrome characterized by persistent airflow restriction which is the result of lung cGVHD. BOS is one of the main causes of late mortality after allo-HSCT, severely restricting the daily activities and respiratory function of patients. It limits the quality of life and increased the non-relapse mortality (NRM) after allo-HSCT. Currently, the first-line treatment for BOS is FAM ( oral fluticasone, azithromycin and montelukast). However, more than 50% of patients develop as steroids resistant (SR)-BOS, and SR-BOS has a poor prognosis and irreversible impaired lung function. Ruxolitinib is an effective drug in the treatment of SR-cGVHD. This is a phase Ⅱ prospective clinical study to explore the efficacy and safety of ruxolitinib as a first-line treatment for newly diagnosed BOS after allo-HSCT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female; 18-65 years old
- •Diagnosis of BOS after allo-HCT defined as the 2014 NIH criteria
- •Life expectancy > 6 months at the time of enrollment
- •At least 4 weeks since initiation of the most recent systemic therapy for cGVHD or BOS
- •The ability to understand and willingness to sign a written consent document
排除标准
- •Recurrent malignancy or disease progression requiring anticancer therapy
- •Currently receiving or have previously received ruxolitinib for chronic GVHD therapy
- •Known history of allergy to ruxolitinib or its excipients
- •Hepatic dysfunction: transaminases (ALT, AST) > 5X ULN and/or total bilirubin > 3X ULN
- •Hematologic dysfunction: absolute neutrophil count <1000/μL, platelet cout <30*10E9/L, and/or Hgb < 8 g/dL
- •Renal dysfunction: calculated creatinine clearance < 30 mL/min (Cockcroft-Gault formula)
- •previously received second-line treatment or any drugs in clinical trials for cGVHD
研究组 & 干预措施
treatment group
Ruxolitinib twice daily treatment, combined with steroids 1mg/kg/day for two weeks, and tampering 0.25 mg/kg/day every week
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
absolute FEV1 increase
时间窗: 3 Months
The proportion of participants with a sustained, absolute FEV1 increase by ≥ 10% after 3 months of treatment with ruxolitinib (compared to baseline measure prior to study enrollment)
次要结局
- treatment failure rate(3 Months)
- absolute FEV1 increase(6 Months, 9 Months, 12 Months and 24 Months)
- Improvements in chronic GVHD organ specific manifestations(6 Months, 9 Months, 12 Months and 24 Months)
- Overall Survival(2 years)
- cGVHD progression-free survival(2 years)
- The incidence and types of serious adverse events(From the start of treatment until 30 days after the end of treatment, up to 2 years)
- The change of systemic corticosteroid dose over time(From the start of treatment until the end of treatment, up to 2 years)