Multi-Institutional Prospective Phase II Study of Montelukast for the Treatment of Bronchiolitis Obliterans Following Allogeneic or Autologous Stem Cell Transplantation in Children and Adults
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Number of Participants With Stable or Improved Predicted Forced Expiratory Volume 1 (FEV-1) With Published Literature
研究概览
简要总结
Background:
Bronchiolitis obliterans is a form of chronic graft-versus-host disease (GVHD) that sometimes develops after stem cell transplantation (SCT) or bone marrow transplantation (BMT).
In bronchiolitis obliterans, immune cells that normally fight infections attack the lungs of the transplant recipient, causing destruction of lung tissue and fibrosis (scarring). When fibrosis develops, the lungs cannot work properly.
Montelukast (Singulair) is a drug that has been used for many years to treat asthma. Its use as a treatment for bronchiolitis obliterans is experimental.
Objectives:
To see if montelukast improves or stabilizes lung function in patients who develop bronchiolitis obliterans after BMT or SCT.
To assess the safety of montelukast in patients with bronchiolitis obliterans after BMT or SCT
To see if montelukast affects the cells that damage the lungs.
To see if montelukast improves other forms of chronic GVHD, quality of life, and overall survival in patients with bronchiolitis obliterans after BMT or SCT.
Eligibility:
Patients 6 years of age and older with bronchiolitis obliterans following stem cell transplantation.
Design:
Patients take one montelukast tablet daily for 6 months and undergo the following procedures during this period:
- Lung function tests. The patient breathes into a machine that measures the amount of air that goes into and out of the lungs. This test is done once a month for 3 months, then at 6 months, 12 months and 24 months.
- Medical history and physical examination at the study site about every 3 months for the first year of the study and then at 12 months and 24 months. Patients also have physical examinations monthly for the first 6 months at their primary doctors office. Tests may include blood and urine tests, chest computed tomography (CT) scans, echocardiogram (heart ultrasound), 2- and 6-minute walk tests, and quality-of-life questionnaires.
- Bronchoalveolar lavage in patients 18 years of age and older. The subject s mouth, nose and airways are numbed with lidocaine. Some patients may need sedation or anesthesia for the procedure. A tube (bronchoscope) is then passed through the nose into the airway, and a small amount of fluid is put into the lung. The fluid is then removed and tested for infections or other lung problems.
- Apheresis to collect white blood cells. Whole blood is collected through a tube inserted into a vein in the arm. The white cells are extracted in a cell separator machine, and the rest of the blood is returned to the body through a tube placed in a vein in the other arm. The cells are used to study GVHD and bronchiolitis obliterans.
- Patients who wish to continue montelukast therapy after 6 months may do so under the care of their primary doctor, if both agree to the continuation....
详细描述
Background:
Bronchiolitis obliterans (BO) is an insidious disease with high mortality following allogeneic blood or marrow transplantation (BMT). There are no consistently effective treatments for BO following BMT and the pathogenesis is largely unknown.
The mechanisms underlying similar immune-mediated lung destructive processes are better elucidated. Rejection following allogeneic lung transplantation and scleroderma lung disease result from analogous immunologically mediated destruction of lung tissue leading to similar pathologic and clinical presentations to post-BMT BO.
Increased leukotriene production has recently been implicated in the development of both post-lung transplant BO and scleroderma lung disease in animal models and patient studies.
Montelukast (singulair) is an approved, well-tolerated, oral agent that inhibits leukotriene action in lung inflammation. This agent has been extensively used in children and adults to treat asthma with an excellent safety profile.
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
- 6 Years 至 80 Years（Child, 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
Montelukast to Treat Bronchiolitis Obliterans
Montelukast for the treatment of BO following allogeneic or autologous stem cell transplant.
干预措施: Singulair (Montelukast Sodium) (Drug)
结局指标
主要结局
Number of Participants With Stable or Improved Predicted Forced Expiratory Volume 1 (FEV-1) With Published Literature
时间窗: 180 days
Responsive disease (RD) will be defined as ≥15% absolute improvement in the percentage predicted FEV-1. Progressive disease (PD) will be defined as \>15% decrease in FEV-1 documented on 2 pulmonary function test (PFT) evaluations greater than 2 weeks apart. Stable disease (SD) will be defined as \<15% change in the absolute FEV-1.
Number of Participants With Improved, Stable or Declined Forced Expiratory Volume 1 (FEV-1) Slope at 6 Months
时间窗: 180 days
FEV-1 slope of decline was generated using regression line of FEV-1 value vs. days post hematopoietic stem cell transplant. Responsive disease (RD) for the slope of FEV-1 change will be an increase in the slope of absolute FEV-1. Progressive disease (PD) for the slope of FEV-1 change will be a decrease in the slope of absolute FEV-1. Stable disease (SD) for the slope of FEV-1 change will be a 0 change in FEV-1 slope.
次要结局
- Number of Participants With Adverse Events(Date treatment consent signed to date off study, approximately 71 months and 17 days)
- Forced Expiratory Volume 1 (FEV-1)/Vital Capacity (VC)(Baseline)
- Percentage Overall 2-Year Survival(2 years)
- Number of Non-Infected Participants at Baseline With Cysteinyl Leukotriene Receptor Expression on Cluster of Differentiation (CD4) and CD8 T Cells, Granulocytes, and Eosinophils in Bronchoalveolar Lavage (BAL) Fluid(Day 1 of study)
研究者
Ronald Gress, M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)