Fluticasone Propionate, Azithromycin, and Montelukast Sodium in Treating Patients With Bronchiolitis Obliterans Who Previously Underwent Stem Cell Transplant (FAM for BOS)

This study is currently recruiting participants.
Verified January 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01307462
First received: March 1, 2011
Last updated: January 10, 2014
Last verified: January 2014
  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
Procedure: pulmonary function testing
Other: questionnaire administration
Procedure: quality-of-life assessment
Other: laboratory biomarker analysis
Genetic: protein analysis
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: Targeted Therapy of Bronchiolitis Obliterans Syndrome

Resource links provided by NLM:


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 ]

Estimated Enrollment: 42
Study Start Date: June 2011
Estimated Primary Completion Date: May 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
Procedure: pulmonary function testing
Correlative studies
Other: questionnaire administration
Ancillary studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies
Genetic: protein analysis
Correlative studies
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 and older
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01307462

Locations
United States, Arizona
Mayo Clinic - Scottsdale Recruiting
Scottsdale, Arizona, United States, 85054
Contact: Mark Palazzo    480-342-2665      
Principal Investigator: Nandita Khera         
United States, California
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Leah S. Galvez    650-725-7951      
Principal Investigator: Laura Johnston         
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Michelle K. Burton    813-745-1537      
Principal Investigator: Joseph Pidala         
United States, Maryland
National Cancer Institute Experimental Transplantation & Immunology Branch Recruiting
Bethesda, Maryland, United States, 20892
Contact: Candice Cottle    301-496-5853      
Principal Investigator: Kirsten M. Williams         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Vincent T. Ho    617-632-3667      
Principal Investigator: Vincent T. Ho         
United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Jenna M. Johnson    612-624-9712      
Principal Investigator: Linda J. Burns         
United States, Missouri
Siteman Cancer Center at Washington University Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Teresa Reineck    314-454-8308      
Principal Investigator: Iskra Pusic         
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Theresa Hodin    716-845-5857    theresa.hodin@RoswellPark.org   
Principal Investigator: George L. Chen         
Weill Cornell Medical College Recruiting
New York, New York, United States, 10065
Contact: Sebastian Mayer    646-962-9345      
Principal Investigator: Sebastian Mayer         
United States, North Carolina
University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: William Wood    919-843-7843      
Principal Investigator: William Wood         
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37232
Contact: Jessica L. Piggee    615-875-6120      
Principal Investigator: Madan H. Jagasia         
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Evangelyn Nkwopara    206-667-6830      
Principal Investigator: Guang-Shing Cheng         
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Barbara L. Davies    414-805-8926      
Principal Investigator: Jeanne Palmer         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
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

No publications provided

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: January 10, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Bronchitis
Bronchiolitis
Bronchiolitis Obliterans
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections
Azithromycin
Fluticasone
Montelukast
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents
Anti-Inflammatory Agents
Leukotriene Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on April 23, 2014