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Targeted Therapy of Bronchiolitis Obliterans Syndrome (FAM for BOS)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01307462
First Posted: March 3, 2011
Last Update Posted: October 4, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Stephanie Lee, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  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: Intervention Model: Single Group Assignment
Masking: None (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:


Further study details as provided by Stephanie Lee, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 36
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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   6 Years to 99 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
Stephanie Lee
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:
Responsible Party: Stephanie Lee, 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 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
U54CA163438 ( U.S. NIH Grant/Contract )
RDCRN 6503 ( Other Identifier: DMCC )
First Submitted: March 1, 2011
First Posted: March 3, 2011
Results First Submitted: January 20, 2017
Results First Posted: October 4, 2017
Last Update Posted: October 4, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: De-identified data are reported in aggregate.

Additional relevant MeSH terms:
Bronchiolitis Obliterans
Bronchiolitis
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