Fluticasone Propionate, Azithromycin, and Montelukast Sodium in Treating Patients With Bronchiolitis Obliterans Who Previously Underwent Stem Cell Transplant (FAM for BOS)
Drug: fluticasone propionate
Drug: montelukast sodium
Procedure: pulmonary function testing
Other: questionnaire administration
Procedure: quality-of-life assessment
Other: laboratory biomarker analysis
Genetic: protein analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Targeted Therapy of Bronchiolitis Obliterans Syndrome|
- Treatment failure [ Time Frame: Within 3 months after initiation of study medications ] [ Designated as safety issue: No ]Must be confirmed by a second PFT 2 weeks after the first measurement. A sustained, absolute decrease (worsening) of the FEV1 by >= 10% predicted in comparison to the baseline FEV1.
- Incidence and types of National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) (v4.0) [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]Grade 3-5 serious adverse events (SAEs) attributable to FAM; and the proportion of subjects who stop each drug during the study period.
- Changes in FEF 25-75, RV, DLCO, FEV1/FVC ratio and FEV1/SVC ratio [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]Will include FEV1 at month 6.
- Changes in blood molecular markers: IL8 (azithromycin), cysteinyl and LTB4 (monteleukast), and IL1B, TNF, and IL6, as well as neutrophil count (fluticasone) [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
- Using the National Institute of Health (NIH) consensus criteria, the proportion of subjects with improvements in other chronic GVHD characteristics [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]Because of the relatively small sample sizes, results will be reported descriptively with 95% confidence intervals.
- Changes in HRQOL, exercise capacity, and symptoms compared to baseline [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]Using the following measurements: Short Form (SF) 36, Functional Assessment of Cancer Therapy (FACT), Human Activity Profile (HAP), chronic GVHD symptom scale for participants >= 18 years of age; Activity Scale for Kids (ASK) for participants < 18 years of age; six minute walk test.
- Total systemic steroid exposure [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
|Study Start Date:||June 2011|
|Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
Experimental: 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.
Drug: fluticasone propionate
Given inhaled PO
Other Names:Drug: montelukast sodium
Other Name: SingulairProcedure: pulmonary function testing
Correlative studiesOther: questionnaire administration
Ancillary studiesProcedure: quality-of-life assessment
Other Name: quality of life assessmentOther: laboratory biomarker analysis
Correlative studiesGenetic: protein analysis
Correlative studiesDrug: azithromycin
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.
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.
III. To determine the change in molecular markers of inflammation and fibrosis in the blood with FAM treatment.
IV. To assess the impact of FAM on other chronic graft-versus-host disease (GVHD) manifestations.
V. To assess the impact of FAM on functional status, and health-related quality of life (HRQOL).
VI. To describe changes in steroid dosing.
Patients receive fluticasone propionate inhaled orally (PO) twice daily (BID), azithromycin PO 3 days a week, and montelukast sodium PO once daily (QD). Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 6 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01307462
|United States, Arizona|
|Mayo Clinic - Scottsdale|
|Scottsdale, Arizona, United States, 85054|
|United States, California|
|Stanford, California, United States, 94305|
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|United States, Maryland|
|National Cancer Institute Experimental Transplantation & Immunology Branch|
|Bethesda, Maryland, United States, 20892|
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|United States, Missouri|
|Siteman Cancer Center at Washington University|
|Saint Louis, Missouri, United States, 63110|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Weill Cornell Medical College|
|New York, New York, United States, 10065|
|United States, North Carolina|
|University of North Carolina at Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37232|
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|United States, Wisconsin|
|Medical College of Wisconsin|
|Milwaukee, Wisconsin, United States, 53226|
|Principal Investigator:||Stephanie Lee||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Study Chair:||Kirsten Williams||National Cancer Institute (NCI)|