Ignite Creation Date:
2024-05-05 @ 7:21 PM
Last Modification Date:
2024-10-26 @ 9:47 AM
Study NCT ID:
NCT00656058
Status:
COMPLETED
Last Update Posted:
2018-04-09
First Post:
2008-04-09
Brief Title:
Montelukast to Treat Bronchiolitis Obliterans
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2018-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
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
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 RVforced vital capacity FVC carbon monoxide diffusing capacity DLC02 FEV-1FVC FEV-1slow 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
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 RVforced vital capacity FVC carbon monoxide diffusing capacity DLC02 FEV-1FVC FEV-1slow 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 08-C-0097 | None | None | None |