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Bronchiolitis ObliteransPhase 2FAM for BOSNCT01307462

Targeted Therapy of Bronchiolitis Obliterans Syndrome

A Phase 2 study testing fluticasone propionate, montelukast sodium and azithromycin in people with Bronchiolitis Obliterans, run by Stephanie Lee at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 6 to 99 years
Conditions the study is for
Bronchiolitis Obliterans
What is being tested?
fluticasone propionate, montelukast sodium and azithromycin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
11 sitesUnited States
Study dates
Jun 2011to Dec 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 to 99 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 18Show fewer
  • 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

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • National Cancer Institute Experimental Transplantation & Immunology Branch

    Bethesda, Maryland, 20892

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Masonic Cancer Center, University of Minnesota

    Minneapolis, Minnesota, 55455

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • Weill Cornell Medical College

    New York, New York, 10065

  • Mayo Clinic - Scottsdale

    Scottsdale, Arizona, 85054

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

  • Siteman Cancer Center at Washington University

    St Louis, Missouri, 63110

  • Stanford University

    Stanford, California, 94305

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

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

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

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. 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.

Being tested
fluticasone propionate, montelukast sodium, azithromycin
Medical subject headings
Bronchiolitis Obliterans

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • fluticasone propionateDrug

    Also called Flonase, Flovent

    Given inhaled PO

  • montelukast sodiumDrug

    Also called Singulair

    Given PO

  • azithromycinDrug

    Also called AzaSite, CP 62993, XZ-450

    Given PO

Study groups in NCT01307462
Study groupRoleWhat they receive
Treatment (BOS therapy)ExperimentalPatients 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.
Receives: Drug: fluticasone propionate; Drug: montelukast sodium; Drug: azithromycin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Within 3 months after initiation of study medications

Secondary outcomes (9)

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

    National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) (v4.0)

    Measured: From baseline to 6 months

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

    Measured: Baseline and 6 months

  3. Changes in Blood Molecular Markers: IL8 (Azithromycin), Cysteinyl and LTB4 (Monteleukast), and IL1B, TNF, and IL6, as Well as Neutrophil Count (Fluticasone)

    Measured: Baseline to 6 months

  4. Number of Subjects With Improvements in Other Chronic GVHD Characteristics

    Only includes subjects who had complete or partial response according to the National Institute of Health (NIH) consensus criteria.

    Measured: Baseline and 3 months

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

    Measured: Baseline to 6 months

  6. Changes in Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)

    SF-36 subscales have min=0 and max=100; results are given as change in 6mo score compared to baseline score, not actual score, and a positive change is correlated with improvement in clinical outcome.

    Measured: Baseline and 6 months

  7. Changes in Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)

    FACT-BMT subscales have various min/max, see below; results are given as change in 6mo score compared to baseline score, not actual score, and a positive change is correlated with improvement in clinical outcome.

    FACT physical well-being (0-28) FACT social/family well-being (0-28) FACT emotional well-being (0-24) FACT functional well-being (0-28) FACT Bone Marrow Transplant (BMT) subscale (0-40) FACT trial outcome index (0-96) FACT-General (G) (0-108) FACT-BMT total (0-148)

    Measured: Baseline and 6 months

  8. Changes in Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP)

    HAP subscales have min=0 and max=94; results are given as change in 6mo score compared to baseline score, not actual score, and a positive change is correlated with improvement in clinical outcome.

    Maximum Activity Score (MAS) is highest item number answered still doing. Represents highest oxygen demanding activity that respondent still performs.

    Adjusted Activity Score (AAS) is MAS minus total number of stopped doing responses below MAS. A measure of usual daily activities.

    Modified AAS is MAS minus total number of stopped doing responses below MAS but not penalized for not doing activities not permitted post transplant. The following items are not counted against the score:11,15,19,20,22,25,34,41,42,47,49,50,52,53,54,57,72,73,77,78.

    Measured: Baseline and 6 months

  9. Changes in Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale

    Lee symptom scale (LSS) has subscales with min=0, max=100; results are given as change in 6mo score compared to baseline score, not actual score, and a negative change is correlated with improvement in clinical outcome.

    Measured: Baseline and 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Mar 2011 (estimated)
  2. Study startJun 2011
  3. Primary completionSep 2014
  4. Study completionDec 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01307462
Sponsor's protocol ID
2367.00
Other IDs
NCI-2011-00203, U54CA163438, RDCRN 6503
Acronym
FAM for BOS
Status last verified
Sep 2017
First submitted
1 Mar 2011
Last updated
4 Oct 2017
Data monitoring committee
Yes
Individual data sharing
No: De-identified data are reported in aggregate.

Publications

  • 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.

    PubMed 26475726

  • 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.

    PubMed 34126278

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing fluticasone propionate, montelukast sodium and azithromycin in people with Bronchiolitis Obliterans, run by Stephanie Lee at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects Who Failed Treatment (time frame: Within 3 months after initiation of study medications). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01307462, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2017.

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