Bronchiolitis ObliteransPhase 2NCT00656058
Montelukast to Treat Bronchiolitis Obliterans
A Phase 2 study testing Singulair (Montelukast Sodium) in people with Bronchiolitis Obliterans and Chronic Graft Versus Host Disease, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Bronchiolitis obliterans is a form of chronic graft-versus-host disease (GVHD) that sometimes develops after stem cell transplantation (SCT) or bone marrow transplantation (BMT). Read more about this study
- Who is it for?
- Ages 6 to 80 years
- Conditions the study is for
- Bronchiolitis Obliterans, Chronic Graft Versus Host Disease, Leukotriene
- What is being tested?
- Singulair (Montelukast Sodium)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jun 2008to 22 Feb 2018
- 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 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age greater than 6 years old.
- Diagnosis of bronchiolitis obliterans after allogeneic or autologous stem cell transplant. The criteria will be based on the definitions created by the National Institutes of Health (NIH) consortium on chronic graft versus host disease (cGVHD). As part of these criterion, for patients without pathologic evidence of BO, one other sign of chronic GVHD must be present. For diagnosis of cGVHD, a minimum of the following must be present: 1) a process distinct from that diagnosed as acute GVHD, 2) the presence of a diagnostic sign or a distinctive sign supported by another clinical or laboratory test, and 3) the exclusion of other pathologies (i.e. recurrent cancer, drug reaction or infection (see Appendix 5a for a list of diagnostic signs.). To meet criteria for a diagnosis of bronchiolitis obliterans, patients must fulfill all 3 criteria. Prior lung tissue biopsy will be analyzed and confirmed to show evidence of bronchiolitis obliterans by the National Cancer Institute (NCI) Laboratory of Pathology if available. If tissue is not available for confirmation, a new biopsy will not be performed.
- For bronchiolitis obliterans:
- Forced expiratory volume 1 (FEV1) less than or equal to 75 percent of predicted by pulmonary function evaluation for height and weight.
- Evidence of air-trapping or small airway thickening or bronchiectasis on high resolution chest computed tomography (CT) and residual volume (RV) or RV/forced vital capacity (FVC) greater than 120 percent and evidence of chronic GVHD of another organ, OR FEV1/ vital capacity (slow or forced VC whichever is larger) ratio less than 5 percent of predicted for age or less than 0.7, OR pathologic evidence of bronchiolar inflammation and obstruction of the lumen consistent with a diagnosis of BO. Pulmonary function tests will utilize body plethysmography not helium studies for pertinent values when there is a discrepancy if available.
- Absence of active infection with appropriate investigation of any clinical symptoms to include radiographic, microbiologic, and pathologic studies as determined by the PI or LAI.
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- Patients must also have 2 PFT measurements with documented FEV1 values greater than 3 months apart to calculate the entry FEV1 slope. All available prior PFTs will be utilized for baseline slope calculation. For adult patients, the absolute FEV1 will be utilized for slope calculation; for pediatric patients, the percent predicted will be used. For patients enrolled after an acute decline following BMT without 2 post-BMT values greater than 3 months apart, the pre-BMT value may be utilized as the first value and the entry PFT value may be the second for the slope calculation. The baseline and 6th-cycle PFT should be done at the accruing site.
- Prior therapy: For patients with a chronic diagnosis of BO who have been on treatments, any prior therapy that has been administered chronically for > 3 months will be acceptable for enrollment as long as the patient has not demonstrated consistent improvement attributed to these agents in a one month (or more) period of observation preceding enrollment. For patients on steroids, a steroid burst exceeding and increase of one half mg/kg/day will be considered for the start of the 3 month monitoring period. Notably, documented intercurrent infections that are treated with antimicrobials that result in improvements to, but not above previous baselines will not be considered an improvement attributable to immunosuppressive therapy. Patients who have had consistent improvements in the months preceding trial entry will not be eligible since there will be no way to discern improvement due to montelukast versus another therapy. Alternatively, a patient with a new diagnosis of bronchiolitis obliterans characterized by a new decrease in FEV1 is also eligible for this study. Notably, patients who have received bronchodilators or other pulmonary therapies may be included in this study as long as montelukast is not part of this regimen.
- Performance status: Karnofsky or Lansky performance status greater than or equal to 40 percent (Appendix 1).
- Ability to give informed consent. For patients less than 18 years of age, their legal guardian must give informed consent. Pediatric patients will be included in an age appropriate discussion in accordance with NIH guidelines or participating institutional guidelines.
- Hepatic function: Patients must have evidence of adequate liver function prior to enrollment defined by total bilirubin less than 3 times the upper limit of normal and transaminases less than 5 times the upper limit of normal for age appropriate indices.
- Cardiac function: Patients must have evidence of adequate cardiac function prior to enrollment defined by ejection fraction greater than 25 percent performed within the last 6 months at NIH and absence of symptoms of cardiac disease at FHCRC, JHH, or Hackensack.
- Pulmonary function: Patients must have an FEV1 greater than or equal to 20 percent predicted for inclusion in this study.
Who cannot join
- Underlying disease status: Patients with tumor burden greater than minimal residual disease (i.e. tumor burden that can only be detected by molecular methods) would be excluded from this study.
- Prior post-transplant treatment with montelukast or zakirlukast within the past 2 months and total duration of therapy does not exceed 3 months.
- Clinically significant systemic illness with manifestations of significant organ dysfunction which in the judgment of Principal or Associate Investigator would render the patient unlikely to tolerate the protocol therapy or complete the study.
- Patients must have been on their current cGVHD therapeutic regimen for at least 3 months with stable or decreasing FEV1 to be eligible for this trial. Any patient who has been on a therapy for less than 3 months for cGVHD will need to be monitored for 3 months without improvement in FEV1 prior to enrollment.
- Ventilated patients are excluded.
- Patients taking rifampin or phenobarbital as these medications alter the metabolism of montelukast.
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- Patients taking greater than one age-appropriate dose of ibuprofen or aspirin containing products per day that inhibit cyclooxygenase will be excluded from this trial. The acceptable upper limit for adult daily doses of aspirin is 650mg/day and 800mg/day of ibuprophen. For children, the acceptable upper limit of ibuprophen is pediatric dose per day (less than 10 mg per kg to a maximum of 800 mg). Children should not take aspirin due to risk of Reye's syndrome unless specifically prescribed by their physician.
- Patients with a history of allergy to montelukast.
- Pregnant females and nursing mothers will be excluded from this trial due to unknown risks to the developing fetus. While on study, patients of child-bearing potential must be able to consent to utilize effective birth control measures.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Multi-Institutional Prospective Phase II Study of Montelukast for the Treatment of Bronchiolitis Obliterans Following Allogeneic or Autologous Stem Cell Transplantation in Children and Adults
Background:
Bronchiolitis obliterans is a form of chronic graft-versus-host disease (GVHD) that sometimes develops after stem cell transplantation (SCT) or bone marrow transplantation (BMT).
Read more
In bronchiolitis obliterans, immune cells that normally fight infections attack the lungs of the transplant recipient, causing destruction of lung tissue and fibrosis (scarring). When fibrosis develops, the lungs cannot work properly.
Montelukast (Singulair) is a drug that has been used for many years to treat asthma. Its use as a treatment for bronchiolitis obliterans is experimental.
Objectives:
To see if montelukast improves or stabilizes lung function in patients who develop bronchiolitis obliterans after BMT or SCT.
To assess the safety of montelukast in patients with bronchiolitis obliterans after BMT or SCT
To see if montelukast affects the cells that damage the lungs.
To see if montelukast improves other forms of chronic GVHD, quality of life, and overall survival in patients with bronchiolitis obliterans after BMT or SCT.
Eligibility:
Patients 6 years of age and older with bronchiolitis obliterans following stem cell transplantation.
Design:
Patients take one montelukast tablet daily for 6 months and undergo the following procedures during this period:
- Lung function tests. The patient breathes into a machine that measures the amount of air that goes into and out of the lungs. This test is done once a month for 3 months, then at 6 months, 12 months and 24 months.
- Medical history and physical examination at the study site about every 3 months for the first year of the study and then at 12 months and 24 months. Patients also have physical examinations monthly for the first 6 months at their primary doctors office. Tests may include blood and urine tests, chest computed tomography (CT) scans, echocardiogram (heart ultrasound), 2- and 6-minute walk tests, and quality-of-life questionnaires.
- Bronchoalveolar lavage in patients 18 years of age and older. The subject s mouth, nose and airways are numbed with lidocaine. Some patients may need sedation or anesthesia for the procedure. A tube (bronchoscope) is then passed through the nose into the airway, and a small amount of fluid is put into the lung. The fluid is then removed and tested for infections or other lung problems.
- Apheresis to collect white blood cells. Whole blood is collected through a tube inserted into a vein in the arm. The white cells are extracted in a cell separator machine, and the rest of the blood is returned to the body through a tube placed in a vein in the other arm. The cells are used to study GVHD and bronchiolitis obliterans.
- Patients who wish to continue montelukast therapy after 6 months may do so under the care of their primary doctor, if both agree to the continuation....
Read the detailed description
Background:
Bronchiolitis obliterans (BO) is an insidious disease with high mortality following allogeneic blood or marrow transplantation (BMT). There are no consistently effective treatments for BO following BMT and the pathogenesis is largely unknown.
The mechanisms underlying similar immune-mediated lung destructive processes are better elucidated. Rejection following allogeneic lung transplantation and scleroderma lung disease result from analogous immunologically mediated destruction of lung tissue leading to similar pathologic and clinical presentations to post-BMT BO.
Increased leukotriene production has recently been implicated in the development of both post-lung transplant BO and scleroderma lung disease in animal models and patient studies.
Montelukast (singulair) is an approved, well-tolerated, oral agent that inhibits leukotriene action in lung inflammation. This agent has been extensively used in children and adults to treat asthma with an excellent safety profile.
Objectives:
To evaluate if montelukast stabilizes or improves pulmonary function in patients with BO after BMT using forced expiratory volume 1 (FEV-1) changes as primary endpoints, and oxygen saturation, pulmonary function test (PFT) parameters (forced expiratory flow (FEF) 25-75, residual volume (RV) and RV/forced vital capacity (FVC), carbon monoxide diffusing capacity (DLC02), FEV-1/FVC, FEV-1/slow vital capacity (SVC) ratio), and timed walk tests as secondary endpoints.
To evaluate the safety of montelukast in the population of patients with BO after BMT.
To investigate if leukotriene elevation contributes to the pathogenesis of BO after BMT by measuring leukotriene levels of the blood, urine, and bronchoalveolar lavage (BAL), and leukotriene surface receptor expression on immune cells before and after montelukast administration.
To determine if montelukast improves other chronic graft versus host disease (cGVHD) manifestations, quality of life, and overall survival.
Eligibility:
Patients greater than or equal to 6 years old with bronchiolitis obliterans following stem cell transplantation for any disease indication may be enrolled.
Design:
This is a prospective phase II study, the primary aim of which is to assess whether montelukast improves or stabilizes the pulmonary function of patients with BO after BMT.
Primary outcome data will be analyzed in 2 ways. 1) The proportion of patients with stable or improved percent predicted of FEV-1 will be compared against benchmark data obtained from a literature review. 2) The slope of FEV-1 before and after the introduction of montelukast will be compared.
Pediatric and adult patients with BO following BMT will receive approved doses of montelukast continuously.
The planned length of the study would be 2 years per patient with primary endpoint at 6 months, permitting sufficient time to determine safety and meet other endpoints.
This phase II trial will be conducted at 2 institutions: National Institutes of Health (NIH) and Fred Hutchinson Cancer Research Center. Forty-five patients will be enrolled on this trial.
- Conditions
- Bronchiolitis Obliterans, Chronic Graft Versus Host Disease, Leukotriene, Montelukast, Stem Cell Transplant
- Being tested
- Singulair (Montelukast Sodium)
- Keywords
- Leukotriene, Chronic Graft-Versus-Host Disease, Montelukast, Stem Cell Transplant, Bronchiolitis Obliterans
- Medical subject headings
- Bronchiolitis Obliterans, Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Singulair (Montelukast Sodium)Drug
Singulair (Montelukast Sodium):5-10 mg (weight based dosing) by mouth (PO) hour of sleep (HS)
| Study group | Role | What they receive |
|---|---|---|
| Montelukast to Treat Bronchiolitis Obliterans | Experimental | Montelukast for the treatment of BO following allogeneic or autologous stem cell transplant. Receives: Drug: Singulair (Montelukast Sodium) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Stable or Improved Predicted Forced Expiratory Volume 1 (FEV-1) With Published Literature
Responsive disease (RD) will be defined as ≥15% absolute improvement in the percentage predicted FEV-1. Progressive disease (PD) will be defined as >15% decrease in FEV-1 documented on 2 pulmonary function test (PFT) evaluations greater than 2 weeks apart. Stable disease (SD) will be defined as <15% change in the absolute FEV-1.
Measured: 180 days
Number of Participants With Improved, Stable or Declined Forced Expiratory Volume 1 (FEV-1) Slope at 6 Months
FEV-1 slope of decline was generated using regression line of FEV-1 value vs. days post hematopoietic stem cell transplant. Responsive disease (RD) for the slope of FEV-1 change will be an increase in the slope of absolute FEV-1. Progressive disease (PD) for the slope of FEV-1 change will be a decrease in the slope of absolute FEV-1. Stable disease (SD) for the slope of FEV-1 change will be a 0 change in FEV-1 slope.
Measured: 180 days
Secondary outcomes (4)
Number of Participants With Adverse Events
Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Measured: Date treatment consent signed to date off study, approximately 71 months and 17 days
Forced Expiratory Volume 1 (FEV-1)/Vital Capacity (VC)
Pulmonary function test performed for eligibility and baseline.
Measured: Baseline
Percentage Overall 2-Year Survival
Percentage of participants alive at 2 years.
Measured: 2 years
Number of Non-Infected Participants at Baseline With Cysteinyl Leukotriene Receptor Expression on Cluster of Differentiation (CD4) and CD8 T Cells, Granulocytes, and Eosinophils in Bronchoalveolar Lavage (BAL) Fluid
Fluid from the bronchoalveolar lavage in adult participants (pediatric optional) will be collected and sent to the lab to be evaluated for infectious diseases by flow cytometry
Measured: Day 1 of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2008 (estimated)
- Study start17 Jun 2008
- Primary completion2 May 2014
- Study completion22 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Bronchiolitis ObliteransStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Ronald Gress, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- Ronald E Gress, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00656058
- Sponsor's protocol ID
- 080097
- Other IDs
- 08-C-0097
- Status last verified
- Apr 2018
- First submitted
- 9 Apr 2008
- Last updated
- 9 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Williams KM, Hnatiuk O, Mitchell SA, Baird K, Gadalla SM, Steinberg SM, Shelhamer J, Carpenter A, Avila D, Taylor T, Grkovic L, Pulanic D, Comis LE, Blacklock-Schuver B, Gress RE, Pavletic SZ. NHANES III equations enhance early detection and mortality prediction of bronchiolitis obliterans syndrome after hematopoietic SCT. Bone Marrow Transplant. 2014 Apr;49(4):561-6. doi: 10.1038/bmt.2013.222. Epub 2014 Jan 13.
PubMed 24419526Oral presentation: "Interim Analysis of a Phase II Trial of Montelukast for the Treatment of Bronchiolitis Obliterans Syndrome after HSCT reveal Immunobiology of Disease American Society of Blood and Marrow Transplantation 2013
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-Institutional Prospective Phase II Study of Montelukast for the Treatment of Bronchiolitis Obliterans Following Allogeneic or Autologous Stem Cell Transplantation in Children and Adults
- ClinicalTrials.gov ID
- NCT00656058
- Acronym / sponsor ID
- 080097
- Conditions
- Bronchiolitis Obliterans, Chronic Graft Versus Host Disease, Leukotriene, Montelukast, Stem Cell Transplant
- Keywords
- Leukotriene, Chronic Graft-Versus-Host Disease, Montelukast, Stem Cell Transplant, Bronchiolitis Obliterans
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 17 Jun 2008 (actual)
- Primary completion
- 2 May 2014 (actual)
- Study completion
- 22 Feb 2018 (actual)
- First posted
- 10 Apr 2008 (estimated)
- Results
- Posted 21 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Bronchiolitis obliterans is a form of chronic graft-versus-host disease (GVHD) that sometimes develops after stem cell transplantation (SCT) or bone marrow transplantation (BMT).
In bronchiolitis obliterans, immune cells that normally fight infections attack the lungs of the transplant recipient, causing destruction of lung tissue and fibrosis (scarring). When fibrosis develops, the lungs cannot work properly.
Montelukast (Singulair) is a drug that has been used for many years to treat asthma. Its use as a treatment for bronchiolitis obliterans is experimental.
Objectives:
To see if montelukast improves or stabilizes lung function in patients who develop bronchiolitis obliterans after BMT or SCT.
To assess the safety of montelukast in patients with bronchiolitis obliterans after BMT or SCT
To see if montelukast affects the cells that damage the lungs.
To see if montelukast improves other forms of chronic GVHD, quality of life, and overall survival in patients with bronchiolitis obliterans after BMT or SCT.
Eligibility:
Patients 6 years of age and older with bronchiolitis obliterans following stem cell transplantation.
Design:
Patients take one montelukast tablet daily for 6 months and undergo the following procedures during this period:
- Lung function tests. The patient breathes into a machine that measures the amount of air that goes into and out of the lungs. This test is done once a month for 3 months, then at 6 months, 12 months and 24 months.
- Medical history and physical examination at the study site about every 3 months for the first year of the study and then at 12 months and 24 months. Patients also have physical examinations monthly for the first 6 months at their primary doctors office. Tests may include blood and urine tests, chest computed tomography (CT) scans, echocardiogram (heart ultrasound), 2- and 6-minute walk tests, and quality-of-life questionnaires.
- Bronchoalveolar lavage in patients 18 years of age and older. The subject s mouth, nose and airways are numbed with lidocaine. Some patients may need sedation or anesthesia for the procedure. A tube (bronchoscope) is then passed through the nose into the airway, and a small amount of fluid is put into the lung. The fluid is then removed and tested for infections or other lung problems.
- Apheresis to collect white blood cells. Whole blood is collected through a tube inserted into a vein in the arm. The white cells are extracted in a cell separator machine, and the rest of the blood is returned to the body through a tube placed in a vein in the other arm. The cells are used to study GVHD and bronchiolitis obliterans.
- Patients who wish to continue montelukast therapy after 6 months may do so under the care of their primary doctor, if both agree to the continuation....
Detailed description
Background:
Bronchiolitis obliterans (BO) is an insidious disease with high mortality following allogeneic blood or marrow transplantation (BMT). There are no consistently effective treatments for BO following BMT and the pathogenesis is largely unknown.
The mechanisms underlying similar immune-mediated lung destructive processes are better elucidated. Rejection following allogeneic lung transplantation and scleroderma lung disease result from analogous immunologically mediated destruction of lung tissue leading to similar pathologic and clinical presentations to post-BMT BO.
Increased leukotriene production has recently been implicated in the development of both post-lung transplant BO and scleroderma lung disease in animal models and patient studies.
Montelukast (singulair) is an approved, well-tolerated, oral agent that inhibits leukotriene action in lung inflammation. This agent has been extensively used in children and adults to treat asthma with an excellent safety profile.
Objectives:
To evaluate if montelukast stabilizes or improves pulmonary function in patients with BO after BMT using forced expiratory volume 1 (FEV-1) changes as primary endpoints, and oxygen saturation, pulmonary function test (PFT) parameters (forced expiratory flow (FEF) 25-75, residual volume (RV) and RV/forced vital capacity (FVC), carbon monoxide diffusing capacity (DLC02), FEV-1/FVC, FEV-1/slow vital capacity (SVC) ratio), and timed walk tests as secondary endpoints.
To evaluate the safety of montelukast in the population of patients with BO after BMT.
To investigate if leukotriene elevation contributes to the pathogenesis of BO after BMT by measuring leukotriene levels of the blood, urine, and bronchoalveolar lavage (BAL), and leukotriene surface receptor expression on immune cells before and after montelukast administration.
To determine if montelukast improves other chronic graft versus host disease (cGVHD) manifestations, quality of life, and overall survival.
Eligibility:
Patients greater than or equal to 6 years old with bronchiolitis obliterans following stem cell transplantation for any disease indication may be enrolled.
Design:
This is a prospective phase II study, the primary aim of which is to assess whether montelukast improves or stabilizes the pulmonary function of patients with BO after BMT.
Primary outcome data will be analyzed in 2 ways. 1) The proportion of patients with stable or improved percent predicted of FEV-1 will be compared against benchmark data obtained from a literature review. 2) The slope of FEV-1 before and after the introduction of montelukast will be compared.
Pediatric and adult patients with BO following BMT will receive approved doses of montelukast continuously.
The planned length of the study would be 2 years per patient with primary endpoint at 6 months, permitting sufficient time to determine safety and meet other endpoints.
This phase II trial will be conducted at 2 institutions: National Institutes of Health (NIH) and Fred Hutchinson Cancer Research Center. Forty-five patients will be enrolled on this trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Montelukast to Treat Bronchiolitis Obliterans | Experimental | Drug: Singulair (Montelukast Sodium)Montelukast for the treatment of BO following allogeneic or autologous stem cell transplant. |
Who may qualify
- Ages
- 6 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Age greater than 6 years old.
- Diagnosis of bronchiolitis obliterans after allogeneic or autologous stem cell transplant. The criteria will be based on the definitions created by the National Institutes of Health (NIH) consortium on chronic graft versus host disease (cGVHD). As part of these criterion, for patients without pathologic evidence of BO, one other sign of chronic GVHD must be present. For diagnosis of cGVHD, a minimum of the following must be present: 1) a process distinct from that diagnosed as acute GVHD, 2) the presence of a diagnostic sign or a distinctive sign supported by another clinical or laboratory test, and 3) the exclusion of other pathologies (i.e. recurrent cancer, drug reaction or infection (see Appendix 5a for a list of diagnostic signs.). To meet criteria for a diagnosis of bronchiolitis obliterans, patients must fulfill all 3 criteria. Prior lung tissue biopsy will be analyzed and confirmed to show evidence of bronchiolitis obliterans by the National Cancer Institute (NCI) Laboratory of Pathology if available. If tissue is not available for confirmation, a new biopsy will not be performed.
- Forced expiratory volume 1 (FEV1) less than or equal to 75 percent of predicted by pulmonary function evaluation for height and weight.
- Evidence of air-trapping or small airway thickening or bronchiectasis on high resolution chest computed tomography (CT) and residual volume (RV) or RV/forced vital capacity (FVC) greater than 120 percent and evidence of chronic GVHD of another organ, OR FEV1/ vital capacity (slow or forced VC whichever is larger) ratio less than 5 percent of predicted for age or less than 0.7, OR pathologic evidence of bronchiolar inflammation and obstruction of the lumen consistent with a diagnosis of BO. Pulmonary function tests will utilize body plethysmography not helium studies for pertinent values when there is a discrepancy if available.
- Absence of active infection with appropriate investigation of any clinical symptoms to include radiographic, microbiologic, and pathologic studies as determined by the PI or LAI.
Key exclusion criteria (9 listed)
- Underlying disease status: Patients with tumor burden greater than minimal residual disease (i.e. tumor burden that can only be detected by molecular methods) would be excluded from this study.
- Prior post-transplant treatment with montelukast or zakirlukast within the past 2 months and total duration of therapy does not exceed 3 months.
- Clinically significant systemic illness with manifestations of significant organ dysfunction which in the judgment of Principal or Associate Investigator would render the patient unlikely to tolerate the protocol therapy or complete the study.
- Patients must have been on their current cGVHD therapeutic regimen for at least 3 months with stable or decreasing FEV1 to be eligible for this trial. Any patient who has been on a therapy for less than 3 months for cGVHD will need to be monitored for 3 months without improvement in FEV1 prior to enrollment.
- Ventilated patients are excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Singulair (Montelukast Sodium)Singulair (Montelukast Sodium):5-10 mg (weight based dosing) by mouth (PO) hour of sleep (HS) | Drug | Montelukast to Treat Bronchiolitis Obliterans |
Primary outcome
Number of Participants With Stable or Improved Predicted Forced Expiratory Volume 1 (FEV-1) With Published Literature
Time frame: 180 days
Responsive disease (RD) will be defined as ≥15% absolute improvement in the percentage predicted FEV-1. Progressive disease (PD) will be defined as >15% decrease in FEV-1 documented on 2 pulmonary function test (PFT) evaluations greater than 2 weeks apart. Stable disease (SD) will be defined as <15% change in the absolute FEV-1.
Number of Participants With Improved, Stable or Declined Forced Expiratory Volume 1 (FEV-1) Slope at 6 Months
Time frame: 180 days
FEV-1 slope of decline was generated using regression line of FEV-1 value vs. days post hematopoietic stem cell transplant. Responsive disease (RD) for the slope of FEV-1 change will be an increase in the slope of absolute FEV-1. Progressive disease (PD) for the slope of FEV-1 change will be a decrease in the slope of absolute FEV-1. Stable disease (SD) for the slope of FEV-1 change will be a 0 change in FEV-1 slope.
4 secondary outcomes
Number of Participants With Adverse Events
Time frame: Date treatment consent signed to date off study, approximately 71 months and 17 days
Forced Expiratory Volume 1 (FEV-1)/Vital Capacity (VC)
Time frame: Baseline
Percentage Overall 2-Year Survival
Time frame: 2 years
Number of Non-Infected Participants at Baseline With Cysteinyl Leukotriene Receptor Expression on Cluster of Differentiation (CD4) and CD8 T Cells, Granulocytes, and Eosinophils in Bronchoalveolar Lavage (BAL) Fluid
Time frame: Day 1 of study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24419526Williams KM, Hnatiuk O, Mitchell SA, Baird K, Gadalla SM, Steinberg SM, Shelhamer J, Carpenter A, Avila D, Taylor T, Grkovic L, Pulanic D, Comis LE, Blacklock-Schuver B, Gress RE, Pavletic SZ. NHANES III equations enhance early detection and mortality prediction of bronchiolitis obliterans syndrome after hematopoietic SCT. Bone Marrow Transplant. 2014 Apr;49(4):561-6. doi: 10.1038/bmt.2013.222. Epub 2014 Jan 13.
- Results publicationOral presentation: "Interim Analysis of a Phase II Trial of Montelukast for the Treatment of Bronchiolitis Obliterans Syndrome after HSCT reveal Immunobiology of Disease American Society of Blood and Marrow Transplantation 2013
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Aphasia, Stroke
Not yet recruiting
A New ECP Protocol for the Treatment of cGVHD
Chronic Graft Versus Host Disease
Active, not recruitingPhase 1/2
Alvelestat (MPH966), an Oral Neutrophil Elastase Inhibitor, in Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation
Chronic Graft vs Host Disease, Chronic Graft-Versus-Host Disease
RecruitingPhase 1
Ex Vivo-Expanded Regulatory T Cells Plus Low-Dose Interleukin-2 for Steroid-Refractory Chronic GVHD
Graft Versus Host Disease (cGvHD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ronald E Gress, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Singulair (Montelukast Sodium) in people with Bronchiolitis Obliterans and Chronic Graft Versus Host Disease, run by National Cancer Institute (NCI) at 1 site 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 13 inclusion and 9 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 9 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 21 Oct 2016). 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 Participants With Stable or Improved Predicted Forced Expiratory Volume 1 (FEV-1) With Published Literature (time frame: 180 days). The study lists 2 primary outcomes in all. 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 NCT00656058, 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 9 Apr 2018.