Targeted Therapy of Bronchiolitis Obliterans Syndrome (FAM for BOS)
|ClinicalTrials.gov Identifier: NCT01307462|
Recruitment Status : Completed
First Posted : March 3, 2011
Results First Posted : October 4, 2017
Last Update Posted : October 4, 2017
|Condition or disease||Intervention/treatment||Phase|
|Bronchiolitis Obliterans||Drug: fluticasone propionate Drug: montelukast sodium Drug: azithromycin||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Fluticasone Propionate, Azithromycin, and Montelukast Sodium in Treating Patients With Bronchiolitis Obliterans Who Previously Underwent Stem Cell Transplant|
|Study Start Date :||June 2011|
|Actual Primary Completion Date :||September 2014|
|Actual Study Completion Date :||December 2015|
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: SingulairDrug: azithromycin
- Number of Subjects Who Failed Treatment [ Time Frame: 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.
- Number of Subjects Who Experienced Grade 3-5 SAEs Attributable to FAM and Number of Subjects Who Stopped FAM as a Result [ Time Frame: From baseline to 6 months ]National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) (v4.0)
- Number of Subjects Who Experienced Statistically Significant Changes in FVC, TLC, RV, DLCO [ Time Frame: 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) [ Time Frame: Baseline to 6 months ]
- Number of Subjects With Improvements in Other Chronic GVHD Characteristics [ Time Frame: Baseline and 3 months ]Only includes subjects who had complete or partial response according to the National Institute of Health (NIH) consensus criteria.
- Number of Subjects Were Able to Reduce Their Systemic Steroid Exposure by >=50% [ Time Frame: Baseline to 6 months ]
- Changes in Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36) [ Time Frame: Baseline and 6 months ]SF-36 subscales have min=0 and max=100; results are given as change in 6mo score compared to baseline score, not actual score, and a positive change is correlated with improvement in clinical outcome.
- Changes in Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT) [ Time Frame: Baseline and 6 months ]
FACT-BMT subscales have various min/max, see below; results are given as change in 6mo score compared to baseline score, not actual score, and a positive change is correlated with improvement in clinical outcome.
FACT physical well-being (0-28) FACT social/family well-being (0-28) FACT emotional well-being (0-24) FACT functional well-being (0-28) FACT Bone Marrow Transplant (BMT) subscale (0-40) FACT trial outcome index (0-96) FACT-General (G) (0-108) FACT-BMT total (0-148)
- Changes in Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP) [ Time Frame: Baseline and 6 months ]
HAP subscales have min=0 and max=94; results are given as change in 6mo score compared to baseline score, not actual score, and a positive change is correlated with improvement in clinical outcome.
Maximum Activity Score (MAS) is highest item number answered still doing. Represents highest oxygen demanding activity that respondent still performs.
Adjusted Activity Score (AAS) is MAS minus total number of stopped doing responses below MAS. A measure of usual daily activities.
Modified AAS is MAS minus total number of stopped doing responses below MAS but not penalized for not doing activities not permitted post transplant. The following items are not counted against the score:11,15,19,20,22,25,34,41,42,47,49,50,52,53,54,57,72,73,77,78.
- Changes in Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale [ Time Frame: Baseline and 6 months ]Lee symptom scale (LSS) has subscales with min=0, max=100; results are given as change in 6mo score compared to baseline score, not actual score, and a negative change is correlated with improvement in clinical outcome.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|
|Weill Cornell Medical College|
|New York, New York, United States, 10065|
|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)|