Does Increasing Immunosuppression Prevent Transplant-associated Lung-disease Triggered by Viral Respiratory Tract Infection Following Allogeneic Stem Cell Transplant? A Pilot Study
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Cumulative incidence of new chronic lung disease
研究概览
简要总结
For many patients with blood cancers, stem cell transplantation from a family member or from an unrelated donor remains the only potentially curative option. Unfortunately, up to 40% of patients develop chronic lung disease after the transplant, which substantially increases the risk of death in the long-term. Currently, patients with transplant-related lung disease are treated with some combination of steroids and other immunosuppressant drugs, but only about 1 out of 5 improve.
The importance of our study is that the investigators aim to prevent the development of transplant-related chronic lung disease in the first place. Because a strong risk factor for such chronic lung disease is a prior viral respiratory tract infection, the investigators think there is a window of opportunity to intervene. As soon as "cold and flu" symptoms start, the investigators will treat patients with a combination of drugs aimed at eliminating damaging immune responses triggered by the virus. In the absence of such treatment, the investigators believe these lung-damaging immune responses would persist even after the virus disappears. Our hope is that preventive treatment might avoid the development of chronic lung disease, and this would substantially increase long-term survival in our transplant patients.
This is a pilot study. Once feasibility is established, the investigators will seek to expand this study into a definitive clinical trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Allogeneic transplant within the prior 1 year
- •Age greater than or equal to 18 years
- •Capable of informed consent
- •Neutrophil engraftment has occurred
- •This is the first clinically-recognized episode of viral respiratory tract infection after transplant
排除标准
- •Proof or high suspicion for bacterial, fungal or any non-viral microorganism causing pneumonia
- •CMV, VZV or HSV pneumonia
- •Prior diagnosis of a chronic transplant-related non-infectious pulmonary complication (ex: BO, COP)
- •Treating physician believes the risk of systemic steroids is too great
- •Currently receiving prednisone at or greater than 0.25 mg/kg/day or the equivalent dose of another steroid
- •Currently receiving pentostatin
- •Mycophenolate initiated de novo or increased within the past 4 weeks
- •Use of inhaled corticosteroids within the past 2 weeks for at least 1 week
- •Haploidentical or T-cell depleted graft
- •Lack of pre-transplant pulmonary function tests
- •Evidence of a prior symptomatic viral respiratory tract infection following transplant, whether treated or not
- •Allergy or adverse reaction to any of the study drugs
- •Relapse or progression of the underlying malignancy
- •Palliative care
研究组 & 干预措施
SAMS
Subjects randomized to the SAMS arm will receive a four-drug combination (Steroids, Azithromycin, Montelukast, and Symbicort).
干预措施: Symbicort (Drug)
SAMS
Subjects randomized to the SAMS arm will receive a four-drug combination (Steroids, Azithromycin, Montelukast, and Symbicort).
干预措施: Prednisone (Drug)
SAMS
Subjects randomized to the SAMS arm will receive a four-drug combination (Steroids, Azithromycin, Montelukast, and Symbicort).
干预措施: Azithromycin (Drug)
SAMS
Subjects randomized to the SAMS arm will receive a four-drug combination (Steroids, Azithromycin, Montelukast, and Symbicort).
干预措施: Montelukast (Drug)
结局指标
主要结局
Cumulative incidence of new chronic lung disease
时间窗: 6 months following diagnosis of the viral respiratory tract infection
The incidence rate of new non-infectious pulmonary complications within the 6 month follow-up period will be calculated. Non-infectious pulmonary complications include new airflow obstruction, new restrictive lung disease, and new mixed obstruction/restriction as measured by spirometry at study enrolment, 2 and 8 weeks following viral infection, and by full pulmonary function tests at 3 and 6 weeks following viral infection.
次要结局
- Prevalence of non-infectious pulmonary complications(6 months following the diagnosis of viral respiratory tract infection)
- Long-term functional impairment as defined by need for supplemental oxygen(6 months post viral respiratory tract infection)
- Patient-perceived long-term functional impairment(6 months post viral respiratory tract infection)
- Time to clearance of viral infection(Every 2 weeks until virus is no longer detectable)
- Incidence of progression to respiratory failure(21 days after enrolment)
- Incidence of bacterial or fungal superinfection(Within 21 days after enrolment)
- Incidence of various other infectious complications(Within 6 months after enrolment)
- Overall survival from date of viral respiratory tract infection(6 months post enrolment)
- Overall survival from date of transplant to end of study follow-up(6 months post enrolment)
- Overall survival at 1 year post-transplant(1 year post-transplant)
- Cumulative incidence of death attributable to transplant associated lung disease(6 months post enrolment)
- Cumulative incidence of death from other causes(6 months post enrolment)
研究者
Elizabeth Krakow
Fellow in Hematopoietic Cell Transplantation
Maisonneuve-Rosemont Hospital