Fluticasone Propionate, Azithromycin, and Montelukast Sodium in Treating Patients With Bronchiolitis Obliterans Who Previously Underwent Stem Cell Transplant
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 11
- 主要终点
- Number of Subjects Who Failed Treatment
研究概览
简要总结
This phase II trial studies how well giving fluticasone propionate, azithromycin, and montelukast sodium (FAM) together works in treating patients with bronchiolitis obliterans who previously underwent stem cell transplant. FAM may be an effective treatment for bronchiolitis obliterans
详细描述
PRIMARY OBJECTIVES:
I. To determine if the combination treatment of FAM administered in post hematopoietic cell transplantation (HCT) recipients after the diagnosis of new onset bronchiolitis obliterans syndrome (BOS) can decrease the rate of treatment failure relative to an estimated historical rate of 40% using current therapies.
SECONDARY OBJECTIVES:
I. To confirm the safety profile of FAM.
II. To describe the effect on other standard pulmonary function test parameters: forced expiratory flow at 25%-75% of forced vital capacity (FVC) (FEF25-75), residual volume (RV), diffusion capacity of carbon monoxide (DLCO), forced expiratory volume in 1 second (FEV1)/FVC ratio and FEV1/slow vital capacity (SVC) ratio with FAM treatment.
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 99 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of BOS after HCT within the 6 months before study enrollment; for this study, BOS is defined as:
- •Forced expiratory volume in 1 second (FEV1) < 75% of the predicted normal and FEV1 to slow or inspiratory vital capacity ratio (FEV1/SVC or FEV1/IVC) =< 0.7, both measured before and after administration of bronchodilator OR
- •Pathologic diagnosis of BOS demonstrated by lung biopsy
- •The baseline absolute FEV1 must be >= 10% lower than the pre-transplant absolute FEV1 as defined by the pre-transplant FEV1 minus the baseline FEV1, both measured before administration of a bronchodilator
- •Participant (or parent/guardian) has the ability to understand and willingness to sign a written consent document
排除标准
- •Recurrent or progressive malignancy requiring anticancer treatment
- •Known history of allergy to or intolerance of montelukast, zafirlukast, azithromycin, erythromycin, or clarithromycin
- •Pregnancy or nursing; all females of childbearing potential must have a negative serum or urine pregnancy test < 7 days before study drug administration
- •Transaminases > 5 X upper limit of normal (ULN)
- •Total bilirubin > 3 X ULN
- •Chronic treatment with any inhaled steroid for > 1 month in the past three months
- •Treatment with montelukast or zafirlukast for > 1 month during the past three months
- •Treatment with prednisone at > 1.2 mg/kg/day (or equivalent steroid)
- •Treatment with rifampin or phenobarbital, aspirin at doses > 325 mg/day, or ibuprofen at doses > 1200 mg/day
- •Treatment with any Food and Drug Administration (FDA) non approved study medication within the past 4 weeks; off-label treatment with an FDA-approved medication is allowed
- •Chronic oxygen therapy
- •Evidence of any viral, bacterial or fungal infection involving the lung and not responding to appropriate treatment
- •Clinical asthma (variable and recurring symptoms of airflow obstruction and bronchial hyper-responsiveness)
- •Any condition that, in the opinion of the enrolling investigator, would interfere with the subject's ability to comply with the study requirements
- •Uncontrolled substance abuse or psychiatric disorder
- •Inability to perform pulmonary function tests (PFT) reliably, as determined by the enrolling investigator or PFT lab
- •Life expectancy < 6 months at the time of enrollment as judged by the enrolling investigator
- •Baseline post-bronchodilator FEV1 < 20% of predicted normal before or after albuterol
研究组 & 干预措施
Treatment (BOS therapy)
Patients receive fluticasone propionate inhaled PO BID, azithromycin PO 3 days a week, and montelukast sodium PO QD. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.
干预措施: fluticasone propionate (Drug)
Treatment (BOS therapy)
Patients receive fluticasone propionate inhaled PO BID, azithromycin PO 3 days a week, and montelukast sodium PO QD. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.
干预措施: montelukast sodium (Drug)
Treatment (BOS therapy)
Patients receive fluticasone propionate inhaled PO BID, azithromycin PO 3 days a week, and montelukast sodium PO QD. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.
干预措施: azithromycin (Drug)
结局指标
主要结局
Number of Subjects Who Failed Treatment
时间窗: Within 3 months after initiation of study medications
Treatment failure is defined as sustained, absolute decrease (worsening) of the FEV1 by \>= 10% predicted in comparison to the baseline FEV1. Must be confirmed by a second PFT 2 weeks after the first measurement.
次要结局
- Number of Subjects Who Experienced Statistically Significant Changes in FVC, TLC, RV, DLCO(Baseline and 6 months)
- Changes in Blood Molecular Markers: IL8 (Azithromycin), Cysteinyl and LTB4 (Monteleukast), and IL1B, TNF, and IL6, as Well as Neutrophil Count (Fluticasone)(Baseline to 6 months)
- Number of Subjects Were Able to Reduce Their Systemic Steroid Exposure by >=50%(Baseline to 6 months)
- Changes in Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale(Baseline and 6 months)
- Changes in Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP)(Baseline and 6 months)
- Number of Subjects Who Experienced Grade 3-5 SAEs Attributable to FAM and Number of Subjects Who Stopped FAM as a Result(From baseline to 6 months)
- Number of Subjects With Improvements in Other Chronic GVHD Characteristics(Baseline and 3 months)
- Changes in Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)(Baseline and 6 months)
- Changes in Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)(Baseline and 6 months)
研究者
Stephanie Lee
Principal Investigator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium