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Montelukast to Treat Bronchiolitis Obliterans

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ClinicalTrials.gov Identifier: NCT00656058
Recruitment Status : Completed
First Posted : April 10, 2008
Results First Posted : October 21, 2016
Last Update Posted : April 9, 2018
Sponsor:
Information provided by (Responsible Party):
Ronald Gress, M.D., National Institutes of Health Clinical Center (CC)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Bronchiolitis Obliterans
Chronic Graft Versus Host Disease
Leukotriene
Montelukast
Stem Cell Transplant
Intervention Drug: Singulair (Montelukast Sodium)
Enrollment 25

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Montelukast to Treat Bronchiolitis Obliterans
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Montelukast for the treatment of BO following allogeneic or autologous stem cell transplant.

Singular (Montelukast Sodium): Singular (Montelukast Sodium):5-10 mg (weight based dosing) PO HS

Period Title: Overall Study
Started 25
Completed 19
Not Completed 6
Reason Not Completed
Withdrawal by Subject             2
Withdrawal by Subject             4
Arm/Group Title Montelukast to Treat Bronchiolitis Obliterans
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Montelukast for the treatment of BO following allogeneic or autologous stem cell transplant.

Singular (Montelukast Sodium): Singular (Montelukast Sodium):5-10 mg (weight based dosing) PO HS

Overall Number of Baseline Participants 25
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
<=18 years
1
   4.0%
Between 18 and 65 years
23
  92.0%
>=65 years
1
   4.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 25 participants
45.29  (15.65)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Female
14
  56.0%
Male
11
  44.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Hispanic or Latino
1
   4.0%
Not Hispanic or Latino
24
  96.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   4.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
2
   8.0%
White
22
  88.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 25 participants
25
 100.0%
1.Primary Outcome
Title Number of Participants With Stable or Improved Predicted Forced Expiratory Volume 1 (FEV-1) With Published Literature
Hide Description 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.
Time Frame 180 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
No data is available for the one missing participant.
Arm/Group Title Montelukast to Treat Bronchiolitis Obliterans
Hide Arm/Group Description:

Montelukast for the treatment of BO following allogeneic or autologous stem cell transplant.

Singular (Montelukast Sodium): Singular (Montelukast Sodium):5-10 mg (weight based dosing) PO HS

Overall Number of Participants Analyzed 19
Measure Type: Count of Participants
Unit of Measure: Participants
Increased 5-13% of predicted
5
  26.3%
Stable
7
  36.8%
Declined
6
  31.6%
Missing
1
   5.3%
2.Primary Outcome
Title Number of Participants With Improved, Stable or Declined Forced Expiratory Volume 1 (FEV-1) Slope at 6 Months
Hide Description 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.
Time Frame 180 days
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Montelukast to Treat Bronchiolitis Obliterans
Hide Arm/Group Description:

Montelukast for the treatment of BO following allogeneic or autologous stem cell transplant.

Singular (Montelukast Sodium): Singular (Montelukast Sodium):5-10 mg (weight based dosing) PO HS

Overall Number of Participants Analyzed 19
Measure Type: Count of Participants
Unit of Measure: Participants
Improved
9
  47.4%
Stable
9
  47.4%
Declined
1
   5.3%
3.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Time Frame Date treatment consent signed to date off study, approximately 71 months and 17 days
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Montelukast to Treat Bronchiolitis Obliterans
Hide Arm/Group Description:

Montelukast for the treatment of BO following allogeneic or autologous stem cell transplant.

Singular (Montelukast Sodium): Singular (Montelukast Sodium):5-10 mg (weight based dosing) PO HS

Overall Number of Participants Analyzed 25
Measure Type: Count of Participants
Unit of Measure: Participants
20
  80.0%
4.Secondary Outcome
Title Forced Expiratory Volume 1 (FEV-1)/Vital Capacity (VC)
Hide Description Pulmonary function test performed for eligibility and baseline.
Time Frame Baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Montelukast to Treat Bronchiolitis Obliterans
Hide Arm/Group Description:

Montelukast for the treatment of BO following allogeneic or autologous stem cell transplant.

Singular (Montelukast Sodium): Singular (Montelukast Sodium):5-10 mg (weight based dosing) PO HS

Overall Number of Participants Analyzed 19
Median (Full Range)
Unit of Measure: Ratio
0.5
(0.29 to 0.78)
5.Secondary Outcome
Title Percentage Overall 2-Year Survival
Hide Description Percentage of participants alive at 2 years.
Time Frame 2 years
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Hide Analysis Population Description
This is a multicenter study and the number analyzed reflect data for evaluable subjects enrolled at the National Institutes of Health only.
Arm/Group Title Montelukast to Treat Bronchiolitis Obliterans
Hide Arm/Group Description:

Montelukast for the treatment of BO following allogeneic or autologous stem cell transplant.

Singular (Montelukast Sodium): Singular (Montelukast Sodium):5-10 mg (weight based dosing) PO HS

Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: percentage of participants
84
6.Secondary Outcome
Title 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
Hide Description 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
Time Frame Day 1 of study
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Montelukast to Treat Bronchiolitis Obliterans
Hide Arm/Group Description:

Montelukast for the treatment of BO following allogeneic or autologous stem cell transplant.

Singular (Montelukast Sodium): Singular (Montelukast Sodium):5-10 mg (weight based dosing) PO HS

Overall Number of Participants Analyzed 19
Measure Type: Count of Participants
Unit of Measure: Participants
19
 100.0%
Time Frame Date treatment consent signed to date off study, approximately 71 months and 17 days.
Adverse Event Reporting Description The serious adverse events while on study are not possibly, probably, or definitely related to montelukast or attributed to research interventions.
 
Arm/Group Title Montelukast to Treat Bronchiolitis Obliterans
Hide Arm/Group Description

Montelukast for the treatment of BO following allogeneic or autologous stem cell transplant.

Singular (Montelukast Sodium): Singular (Montelukast Sodium):5-10 mg (weight based dosing) PO HS

All-Cause Mortality
Montelukast to Treat Bronchiolitis Obliterans
Affected / at Risk (%)
Total   3/25 (12.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Montelukast to Treat Bronchiolitis Obliterans
Affected / at Risk (%) # Events
Total   15/25 (60.00%)    
Gastrointestinal disorders   
Anorexia  1  1/25 (4.00%)  1
Dehydration  1  1/25 (4.00%)  1
Diarrhea  1  1/25 (4.00%)  1
Gastrointestinal - Other (gastroenteritis)  1  1/25 (4.00%)  1
Hemorrhage, GI::Abdomen NOS  1  1/25 (4.00%)  1
Vomiting  1  1/25 (4.00%)  1
General disorders   
Death not associated with CTCAE term::Death NOS  1  2/25 (8.00%)  2
Death not associated with CTCAE term::Multi-organ failure  1  1/25 (4.00%)  1
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)  1  1/25 (4.00%)  1
Hepatobiliary disorders   
Pancreatitis  1  1/25 (4.00%)  1
Infections and infestations   
Infection - Other (CMV reactivation)  1  1/25 (4.00%)  2
Infection - Other (pneumonia/infection with unknown ANC)  1  1/25 (4.00%)  1
Infection - Other (sinusitis)  1  1/25 (4.00%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils::Lung (pneumonia)  1  4/25 (16.00%)  5
Infection with normal ANC or Grade 1 or 2 neutrophils::Upper airway NOS  1  1/25 (4.00%)  4
Infection with unknown ANC::Colon  1  1/25 (4.00%)  1
Infection with unknown ANC::Lung (pneumonia)  1  1/25 (4.00%)  1
Infection with unknown ANC::Urinary tract NOS  1  1/25 (4.00%)  1
Musculoskeletal and connective tissue disorders   
Joint-effusion  1  1/25 (4.00%)  1
Nervous system disorders   
Mood alteration::Depression  1  1/25 (4.00%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnea (shortness of breath)  1  2/25 (8.00%)  2
Hypoxia  1  3/25 (12.00%)  3
Parainfluenza Pneumonia  1  1/25 (4.00%)  1
Pneumonitis/pulmonary infiltrates  1  1/25 (4.00%)  1
RSV Pneumonia  1  1/25 (4.00%)  1
Skin and subcutaneous tissue disorders   
Urticaria (hives, welts, wheals)  1  1/25 (4.00%)  1
Vascular disorders   
Thrombosis/embolism (vascular access-related)  1  1/25 (4.00%)  1
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Montelukast to Treat Bronchiolitis Obliterans
Affected / at Risk (%) # Events
Total   16/25 (64.00%)    
Blood and lymphatic system disorders   
Edema: limb  1  1/25 (4.00%)  1
Hemoglobin  1  2/25 (8.00%)  2
Leukocytes (total WBC)  1  1/25 (4.00%)  1
Lymphopenia  1  1/25 (4.00%)  3
Gastrointestinal disorders   
Gastrointestinal - Other (Pneumatosis coli)  1  1/25 (4.00%)  1
Mucositis/stomatitis (clinical exam)::Oral cavity  1  1/25 (4.00%)  1
Nausea  1  1/25 (4.00%)  1
General disorders   
Weight loss  1  2/25 (8.00%)  2
Infections and infestations   
Infection  1 [1]  1/25 (4.00%)  1
Infection - Other (Helicobacter pylori infection)  1  1/25 (4.00%)  1
Infection - Other (S. Maltophilia)  1  1/25 (4.00%)  1
Infection - Other (URI)  1  1/25 (4.00%)  1
Infection - Other (Viral infection (evaluated by home physicians))  1  1/25 (4.00%)  1
Infection - Other (fever and URI symptoms)  1  1/25 (4.00%)  2
Infection - Other (upper respiratory infection)  1  1/25 (4.00%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils::Bronchus  1  1/25 (4.00%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils::Upper airway NOS  1  2/25 (8.00%)  2
Infection with unknown ANC::Lung (pneumonia)  1  1/25 (4.00%)  1
Infection with unknown ANC::Sinus  1  1/25 (4.00%)  1
Metabolism and nutrition disorders   
ALT, SGPT (serum glutamic pyruvic transaminase)  1  4/25 (16.00%)  5
AST, SGOT(serum glutamic oxaloacetic transaminase)  1  4/25 (16.00%)  5
Albumin, serum-low (hypoalbuminemia)  1  4/25 (16.00%)  5
Alkaline phosphatase  1  1/25 (4.00%)  2
GGT (gamma-Glutamyl transpeptidase)  1  1/25 (4.00%)  1
Lipase  1  1/25 (4.00%)  1
Phosphate, serum-low (hypophosphatemia)  1  4/25 (16.00%)  5
Potassium, serum-high (hyperkalemia)  1  2/25 (8.00%)  3
Potassium, serum-low (hypokalemia)  1  1/25 (4.00%)  1
Sodium, serum-low (hyponatremia)  1  1/25 (4.00%)  1
Triglyceride, serum-high (hypertriglyceridemia)  1  1/25 (4.00%)  1
Musculoskeletal and connective tissue disorders   
Muscle weakness, generalized or specific area (not due to neuropathy)::Extremity-lower  1  1/25 (4.00%)  1
Pain: joint  1  1/25 (4.00%)  1
Nervous system disorders   
Neuropathy: sensory  1  1/25 (4.00%)  1
Neutrophils/granulocytes (ANC/AGC)  1  1/25 (4.00%)  1
Psychiatric disorders   
Psychosis (hallucinations/delusions)  1  1/25 (4.00%)  1
Renal and urinary disorders   
Renal/Genitourinary - Other (interstitial renal fibrosis)  1  1/25 (4.00%)  1
Urinary frequency/urgency  1  1/25 (4.00%)  1
Respiratory, thoracic and mediastinal disorders   
Cough  1  2/25 (8.00%)  3
Hemorrhage, pulmonary/upper respiratory::Lung  1  1/25 (4.00%)  2
Hypoxia  1  1/25 (4.00%)  1
Pain::Chest/thorax NOS  1  1/25 (4.00%)  1
Pulmonary/Upper Respiratory - Other (URI)  1  1/25 (4.00%)  2
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
[1]
(documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L)::Lung (pneumonia)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Ronald E. Gress
Organization: National Cancer Institute
Phone: 301-496-1791
Publications of Results:
Oral 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
Responsible Party: Ronald Gress, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00656058     History of Changes
Other Study ID Numbers: 080097
08-C-0097
First Submitted: April 9, 2008
First Posted: April 10, 2008
Results First Submitted: August 29, 2016
Results First Posted: October 21, 2016
Last Update Posted: April 9, 2018