Targeted Therapy of Bronchiolitis Obliterans Syndrome

NCT01307462 | Completed Phase 2 Results DMC

• 4 other identifiers: 2367.00NCI-2011-00203U54CA163438RDCRN 6503
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 11

Brief Summary

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

Conditions

Bronchiolitis Obliterans

Outcome Measures

Primary Outcomes (1)

• Number of Subjects Who Failed Treatment

  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.

  Within 3 months after initiation of study medications

Secondary Outcomes (9)

• Number of Subjects Who Experienced Grade 3-5 SAEs Attributable to FAM and Number of Subjects Who Stopped FAM as a Result

  From baseline to 6 months

• Number of Subjects Who Experienced Statistically Significant Changes in FVC, TLC, RV, DLCO

  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)

  Baseline to 6 months

• Number of Subjects With Improvements in Other Chronic GVHD Characteristics

  Baseline and 3 months

• Number of Subjects Were Able to Reduce Their Systemic Steroid Exposure by >=50%

  Baseline to 6 months

Study Arms (1)

Treatment (BOS therapy)

EXPERIMENTAL

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; Drug: montelukast sodium; Drug: azithromycin

Interventions

fluticasone propionate DRUG

Given inhaled PO

Also known as: Flonase, Flovent

Treatment (BOS therapy)

montelukast sodium DRUG

Given PO

Also known as: Singulair

Treatment (BOS therapy)

azithromycin DRUG

Given PO

Also known as: AzaSite, CP 62993, XZ-450

Treatment (BOS therapy)

Eligibility Criteria

• Age: 6 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Stephanie Lee: lead
• National Cancer Institute (NCI): collaborator

Study Sites (11)

Mayo Clinic - Scottsdale

Scottsdale, Arizona, 85054, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

National Cancer Institute Experimental Transplantation & Immunology Branch

Bethesda, Maryland, 20892, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Siteman Cancer Center at Washington University

St Louis, Missouri, 63110, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (2)

• 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 MED, 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):710-716. doi: 10.1016/j.bbmt.2015.10.009. Epub 2015 Oct 22.

  PMID: 26475726 RESULT

• Inamoto Y, Martin PJ, Onstad LE, Cheng GS, Williams KM, Pusic I, Ho VT, Arora M, Pidala J, Flowers MED, Gooley TA, Lawler RL, Hansen JA, Lee SJ. Relevance of Plasma Matrix Metalloproteinase-9 for Bronchiolitis Obliterans Syndrome after Allogeneic Hematopoietic Cell Transplantation. Transplant Cell Ther. 2021 Sep;27(9):759.e1-759.e8. doi: 10.1016/j.jtct.2021.06.006. Epub 2021 Jun 12.

  PMID: 34126278 DERIVED

MeSH Terms

Conditions

Bronchiolitis Obliterans

Interventions

Fluticasone; montelukast; Azithromycin

Condition Hierarchy (Ancestors)

Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Guang-Shing Cheng MD
• Organization: FHCRC

gcheng2@fhcrc.org

206-667-7074

Study Officials

• Stephanie Lee

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

• Kirsten Williams

  National Cancer Institute (NCI)

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 1, 2011
• First Posted: March 3, 2011
• Study Start: June 1, 2011
• Primary Completion: September 1, 2014
• Study Completion: December 1, 2015
• Last Updated: October 4, 2017
• Results First Posted: October 4, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)