Vanderbilt-Ingram Cancer Center

Participants are being asked to take part in this research study because they have received a hematopoietic cell transplant (HCT) and developed Bronchiolitis Obliterans Syndrome (BOS) less than 3 months ago. BOS occurs in up to 4-8% of HCT patients. BOS makes it very hard for air to pass through the lungs. Symptoms of BOS may include dry cough (60-100%), difficulty breathing (50-70%), and wheezing (40%). BOS may decrease quality of life and increase the chance of death after transplant. The current way to treat BOS is to use high doses of steroids (a type of drug) for as long as one year. Long term steroid use can result in bone damage and serious infections. Study doctors want to find a better way to treat BOS that does not require high doses of steroids.

Criteria
 Inclusion Criteria:

 • 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

 Exclusion Criteria:

 • 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