Targeted Therapy of Bronchiolitis Obliterans Syndrome - Full Text View

Purpose

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

Condition	Intervention	Phase
Bronchiolitis Obliterans	Drug: fluticasone propionate Drug: montelukast sodium Drug: azithromycin	Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Fluticasone Propionate, Azithromycin, and Montelukast Sodium in Treating Patients With Bronchiolitis Obliterans Who Previously Underwent Stem Cell Transplant

Resource links provided by NLM:

Drug Information available for: Fluticasone propionate Azithromycin Fluticasone Montelukast sodium Montelukast Fluticasone furoate

Genetic and Rare Diseases Information Center resources: Bronchiolitis Obliterans

U.S. FDA Resources

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:

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.

Secondary Outcome Measures:

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 ]


Enrollment:	5
Study Start Date:	June 2011
Study Completion Date:	December 2015
Primary Completion Date:	September 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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: Flonase Flovent Drug: montelukast sodium Given PO Other Name: Singulair Drug: azithromycin Given PO Other Names: AzaSite CP 62993 XZ-450

Detailed Description:

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.

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.

OUTLINE:

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.

Eligibility


Ages Eligible for Study:	6 Years to 99 Years (Child, Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01307462

Locations


United States, Arizona
Mayo Clinic - Scottsdale
Scottsdale, Arizona, United States, 85054
United States, California
Stanford University
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
Vanderbilt University
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

Sponsors and Collaborators

Lee, Stephanie

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Stephanie Lee	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Study Chair:	Kirsten Williams	National Cancer Institute (NCI)

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Williams KM, Cheng GS, Pusic I, Jagasia M, Burns L, Ho VT, Pidala J, Palmer J, Johnston L, Mayer S, Chien JW, Jacobsohn DA, Pavletic SZ, Martin PJ, Storer BE, Inamoto Y, Chai X, Flowers ME, Lee SJ. Fluticasone, Azithromycin, and Montelukast Treatment for New-Onset Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2016 Apr;22(4):710-6. doi: 10.1016/j.bbmt.2015.10.009. Epub 2015 Oct 22.


Responsible Party:	Lee, Stephanie, Principal Investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
ClinicalTrials.gov Identifier:	NCT01307462 History of Changes
Other Study ID Numbers:	2367.00 NCI-2011-00203 U54CA163438 RDCRN 6503
Study First Received:	March 1, 2011
Last Updated:	August 9, 2016
Health Authority:	United States: Food and Drug Administration
Individual Participant Data
Plan to Share IPD:	No
Plan Description:	De-identified data are reported in aggregate.

Additional relevant MeSH terms:


Bronchiolitis Bronchiolitis Obliterans Bronchitis Bronchial Diseases Respiratory Tract Diseases Lung Diseases, Obstructive Lung Diseases Respiratory Tract Infections Fluticasone Montelukast Anti-Inflammatory Agents Bronchodilator Agents Autonomic Agents	Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Asthmatic Agents Respiratory System Agents Dermatologic Agents Anti-Allergic Agents Leukotriene Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Cytochrome P-450 CYP1A2 Inducers Cytochrome P-450 Enzyme Inducers Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 26, 2016

Targeted Therapy of Bronchiolitis Obliterans Syndrome (FAM for BOS)