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Targeted Therapy of Bronchiolitis Obliterans Syndrome


Phase 2
6 Years
N/A
Open (Enrolling)
Both
Bronchiolitis Obliterans

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Trial Information

Targeted Therapy of Bronchiolitis Obliterans Syndrome


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.


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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Treatment failure

Outcome Description:

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.

Outcome Time Frame:

Within 3 months after initiation of study medications

Safety Issue:

No

Principal Investigator

Stephanie Lee

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Food and Drug Administration

Study ID:

2367.00

NCT ID:

NCT01307462

Start Date:

June 2011

Completion Date:

Related Keywords:

  • Bronchiolitis Obliterans
  • Bronchiolitis
  • Bronchiolitis Obliterans

Name

Location

H. Lee Moffitt Cancer Center and Research InstituteTampa, Florida  33612
Medical College of WisconsinMilwaukee, Wisconsin  53226
Stanford UniversityStanford, California  94305
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
Vanderbilt UniversityNashville, Tennessee  37232-6305
University of North Carolina at Chapel HillChapel Hill, North Carolina  27599
Masonic Cancer Center, University of MinnesotaMinneapolis, Minnesota  55455
Weill Cornell Medical CollegeNew York, New York  10021
Mayo Clinic - ScottsdaleScottsdale, Arizona  85259
National Cancer Institute Experimental Transplantation & Immunology BranchBethesda, Maryland  20892
Siteman Cancer Center at Washington UniversitySaint Louis, Missouri  63110