Targeted Therapy of Bronchiolitis Obliterans Syndrome

NCT ID: NCT01307462

Last Updated: 2017-10-04

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-06-30

Study Completion Date

2015-12-31

Brief Summary

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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

Detailed Description

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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.

Conditions

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Bronchiolitis Obliterans

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

fluticasone propionate

Intervention Type DRUG

Given inhaled PO

montelukast sodium

Intervention Type DRUG

Given PO

azithromycin

Intervention Type DRUG

Given PO

Interventions

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fluticasone propionate

Given inhaled PO

Intervention Type DRUG

montelukast sodium

Given PO

Intervention Type DRUG

azithromycin

Given PO

Intervention Type DRUG

Other Intervention Names

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Flonase Flovent Singulair AzaSite CP 62993 XZ-450

Eligibility Criteria

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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
Minimum Eligible Age

6 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Stephanie Lee

OTHER

Sponsor Role lead

Responsible Party

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Stephanie Lee

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Stephanie Lee

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Kirsten Williams

Role: STUDY_CHAIR

National Cancer Institute (NCI)

Locations

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Mayo Clinic - Scottsdale

Scottsdale, Arizona, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Site Status

National Cancer Institute Experimental Transplantation & Immunology Branch

Bethesda, Maryland, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Siteman Cancer Center at Washington University

St Louis, Missouri, United States

Site Status

Weill Cornell Medical College

New York, New York, United States

Site Status

Vanderbilt University

Nashville, Tennessee, United States

Site Status

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 26475726 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34126278 (View on PubMed)

Other Identifiers

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NCI-2011-00203

Identifier Type: REGISTRY

Identifier Source: secondary_id

U54CA163438

Identifier Type: NIH

Identifier Source: secondary_id

View Link

RDCRN 6503

Identifier Type: OTHER

Identifier Source: secondary_id

2367.00

Identifier Type: -

Identifier Source: org_study_id