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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01307462
First received: March 1, 2011
Last updated: August 4, 2014
Last verified: August 2014

March 1, 2011
August 4, 2014
June 2011
September 2014   (final data collection date for primary outcome measure)
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.
Treatment failure [ Time Frame: Within 3 months after initiation of study medications and confirmed by a second PFT 2 weeks after the first measurement ] [ Designated as safety issue: No ]
A sustained, absolute decrease (worsening) of the FEV1 by >= 10% predicted in comparison to the baseline FEV1
Complete list of historical versions of study NCT01307462 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Incidence and types of National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) (v3.0) [ Time Frame: At months 1, 2, 3, and 6 ] [ Designated as safety issue: Yes ]
  • Changes in FEF 25-75, RV, DLCO, FEV1/FVC ratio and FEV1/SVC ratio [ Time Frame: At months 3 and 6 (including FEV1 at month 6) ] [ Designated as safety issue: No ]
  • Changes in blood molecular markers: IL8 (azithromycin), cysteinyl and LTB4 (monteleukast), and IL1B, TNF, and IL6, as well as neutrophil count (fluticasone) [ Time Frame: At month 3 and month 6 ] [ 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: At month 3 and month 6 ] [ Designated as safety issue: No ]
  • Changes in HRQOL, exercise capacity, and symptoms compared to baseline [ Time Frame: At month 3 and month 6 ] [ Designated as safety issue: No ]
  • Total systemic steroid exposure [ Time Frame: By month 3 and month 6 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Fluticasone Propionate, Azithromycin, and Montelukast Sodium in Treating Patients With Bronchiolitis Obliterans Who Previously Underwent Stem Cell Transplant
Targeted Therapy of Bronchiolitis Obliterans Syndrome

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

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Bronchiolitis Obliterans
  • 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
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.
Interventions:
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
42
Not Provided
September 2014   (final data collection date for primary outcome measure)

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
Both
6 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01307462
2367.00, NCI-2011-00203, U54CA163438, RDCRN 6503
Yes
Not Provided
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Principal Investigator: Stephanie Lee Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Study Chair: Kirsten Williams National Cancer Institute (NCI)
Fred Hutchinson Cancer Research Center
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP