Fluticasone Propionate, Azithromycin, and Montelukast Sodium in Treating Patients With Bronchiolitis Obliterans Who Previously Underwent Stem Cell Transplant

Condition(s) targeted: Bronchiolitis Obliterans

Intervention: fluticasone propionate (Drug); montelukast sodium (Drug); pulmonary function testing (Procedure); questionnaire administration (Other); quality-of-life assessment (Procedure); laboratory biomarker analysis (Other); protein analysis (Genetic); azithromycin (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Official(s) and/or principal investigator(s):
Kirsten Williams, Principal Investigator, Affiliation: National Cancer Institute (NCI)
Kirsten Williams, Study Chair, Affiliation: National Cancer Institute (NCI)

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

Official title: Targeted Therapy of Bronchiolitis Obliterans Syndrome

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Treatment failure

Secondary outcome:

Incidence and types of National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) (v3.0)

Changes in FEF 25-75, RV, DLCO, FEV1/FVC ratio and FEV1/SVC ratio

Changes in FEF 25-75, RV, DLCO, FEV1/FVC ratio and FEV1/SVC ratio

Changes in blood molecular markers: IL8 (azithromycin), cysteinyl and LTB4 (montelukast), and IL1B, TNF, and IL6, as well as neutrophil count (fluticasone)

Changes in blood molecular markers: IL8 (azithromycin), cysteinyl and LTB4 (montelukast), and IL1B, TNF, and IL6, as well as neutrophil count (fluticasone)

Using the National Institute of Health (NIH) consensus criteria, the proportion of subjects with improvements in other chronic GVHD characteristics

Using the National Institute of Health (NIH) consensus criteria, the proportion of subjects with improvements in other chronic GVHD characteristics

Changes in HRQOL, exercise capacity, and symptoms compared to baseline

Changes in HRQOL, exercise capacity, and symptoms compared to baseline

Total systemic steroid exposure

Total systemic steroid exposure

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.

Minimum age: 6 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Diagnosis of BOS after HCT within the 3 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 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

- Prophylactic treatment with azithromycin >= 3 x/week for > 1 month during the past

three months; patients that have taken a Z-pak or other macrolides to treat infection are eligible

- 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

Stanford University, Stanford, California 94305, United States; Recruiting
Leah Galvez, Phone: 650-725-7951
Laura Johnston, Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, United States; Recruiting
Michelle Burton, Phone: 813-745-1537
Joseph Pidala, Principal Investigator

National Cancer Institute Experimental Transplantation & Immunology Branch, Bethesda, Maryland 20892, United States; Recruiting
Aisha Wellington, Phone: 301-496-5853, Email: aisha.wellington@nih.gov
Kirsten M. Williams, Principal Investigator

Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States; Recruiting
Eileen Hansen, Phone: 617-632-6715
Vincent T. Ho, Principal Investigator

Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, United States; Recruiting
Jenna M. Johnson, Phone: 612-624-9712, Email: joh03025@umn.edu
Linda Burns, Principal Investigator

Siteman Cancer Center at Washington University, Saint Louis, Missouri 63110, United States; Recruiting
Teresa Reineck, Phone: 314-454-8308, Email: treineck@dom.wustl.edu
Iskra Pusic, Principal Investigator

Vanderbilt University, Nashville, Tennessee 37232, United States; Recruiting
Jessica L. Piggee, Phone: 615-875-6120, Email: jessica.l.piggee@Vanderbilt.edu
Madan H. Jagasia, Principal Investigator

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium, Seattle, Washington 98109, United States; Recruiting
Katie L. Lyon, Phone: 206-667-6830, Email: klaigo@fhcrc.org
Paul J. Martin, Principal Investigator

Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States; Recruiting
Barbara Davies, Phone: 414-805-8926, Email: bdavies@mcw.edu
Jeanne Palmer, Principal Investigator

Starting date: June 2011
Last updated: September 24, 2012