Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Montelukast in Treating Patients With Bronchiolitis Obliterans After Donor Stem Cell Transplant

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Supportive care Active 6 to 80 NCI NCI-08-C-0097 08-C-0097, NCI-P07261, NCT00656058

Special Category: NIH Clinical Center trial

Objectives

Primary

1. To determine if montelukast sodium results in stabilization or improvement in pulmonary function in patients with bronchiolitis obliterans following allogeneic stem cell transplantation by comparing the absolute change in predicted FEV₁ in these patients with a benchmark control from publications and by comparing the FEV₁ slope (of the absolute value) before and after treatment with montelukast sodium.

Secondary

1. To confirm the safety profile of montelukast sodium in these patients.
2. To determine if montelukast sodium improves oxygen saturation or decreases oxygen requirement in these patients.
3. To assess if montelukast sodium improves other pulmonary function parameters, including FEF25-75, RV, DLC02, and the ratio of FEV₁/FVC and FEV₁/SVC, in these patients.
4. To determine if montelukast sodium improves pulmonary endurance in these patients as measured by a 2- and 6-minute walk test.
5. To evaluate if montelukast sodium decreases leukotriene levels (LTB4 and CysLT) in the urine or blood or leukotriene receptor expression (BLT or CysLT) on activated circulating immune cells.
6. To determine if improvement in pulmonary function correlates with decreased leukotriene levels or leukotriene receptor expression on activated circulating immune cells.
7. To investigate whether patients experience improvements in other chronic graft-versus-host disease manifestations and quality of life and function parameters during treatment with montelukast sodium.
8. To evaluate if the introduction of montelukast sodium impacts the 2-year overall survival of these patients.

Entry Criteria

Disease Characteristics:

• Diagnosis of bronchiolitis obliterans (BO) following allogeneic stem cell transplantation, meeting all of the following criteria:
  • FEV₁ < 75% of predicted by pulmonary function test (PFT) for height and weight
    • Patients must have 2 PFT measurements with documented FEV₁ values > 3 months apart to calculate the FEV₁ slope at study entry
  • Meets one of the following criteria:
    • Evidence of air-trapping or small airway thickening or bronchiectasis on high resolution chest CT scan; RV or RV/FVC > 120%; and evidence of chronic graft-vs-host disease (cGVHD) of another organ
    • FEV₁/SVC ratio < 5% of predicted for age or < 0.7
    • Pathologic evidence of bronchiolar inflammation and obstruction of the lumen consistent with a diagnosis of BO
  • No active infection
    • Any clinical symptoms must be evaluated by radiographic, microbiologic, and pathologic studies as determined by the Principal Investigator or Lead Associate Investigator



• Patients without pathologic evidence of BO must have one other sign of cGVHD present
  • For diagnosis of cGVHD, a minimum of the following must be present:
    • A process distinct from that diagnosed as acute GVHD
    • Presence of a diagnostic sign or a distinctive sign supported by another clinical or laboratory test
    • Exclusion of other pathologies (i.e., recurrent cancer, drug reaction, or infection)



• Has been on a therapeutic regimen for cGVHD for ≥ 3 months AND has stable or decreasing FEV₁
  • Any patient who has been on a therapy for cGVHD for < 3 months will need to be monitored for 3 months AND demonstrate no improvement in FEV₁ prior to study enrollment



• No tumor burden greater than minimal residual disease (i.e., tumor burden that can only be detected by molecular methods)

Prior/Concurrent Therapy:

• See Disease Characteristics
• Any prior therapy that has been administered chronically for > 3 months for BO is allowed provided the patient has not demonstrated improvement on this agent during a 1-month period (or longer) of observation prior to study enrollment
• Prior montelukast sodium or zafirlukast allowed provided the patient has been off treatment for at least 2 months prior to study and duration of total therapy did not exceed 3 months
• Prior bronchodilators or other pulmonary therapies allowed
• No concurrent rifampin or phenobarbital
• No concurrent ibuprofen or acetylsalicylic acid (aspirin)-containing products that inhibit cyclooxygenase

Patient Characteristics:

• Karnofsky or Lansky performance status 40-100%
• Total bilirubin < 3 times upper limit of normal (ULN) for age
• Transaminases < 5 times ULN for age
• LVEF > 25%
• FEV₁ ≥ 20% of predicted
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No requirement for ventilation
• No clinically significant systemic illness with manifestations of significant organ dysfunction that, in the judgment of Principal or Associate Investigator, would render the patient unlikely to tolerate study therapy or complete the study
• No history of allergy to montelukast sodium

Expected Enrollment

Outcomes

Comparison of the proportion of patients with stable or improved percentage of predicted FEV1 with published literature
Comparison of the slope of FEV1 before and after treatment with montelukast sodium

Oxygen saturation and supplementation
Pulmonary function tests, including FEF25-75, RV or RV/FVC, DLCO2, and the ratio of FEV1/FVC and FEV1/SVC
Pulmonary endurance as measured by a 2- and 6-minute walk test
Leukotriene levels in the urine and blood and leukotriene receptor expression on activated circulating immune cells
Other chronic graft-vs-host disease manifestations
Quality of life and function parameters
Overall survival at 2 years

Outline

This is a multicenter study.

Patients receive oral montelukast sodium once daily for 6 months in the absence of disease progression or unacceptable toxicity.

Blood and urine samples are collected at baseline and at 3 and 6 months to measure leukotriene levels (cysteinyl and LTB4); leukotriene receptor expression on circulating immune cells (including T-cells, B-cells, eosinophils, neutrophils, and monocytes) by flow cytometry; and cytokine levels by immunofluorescent techniques.

Patients complete quality-of-life questionnaires at baseline and at 1, 3, 6, 12, and 24 months.

After completion of study treatment, patients are followed at 1 and 2 years.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Ronald Gress, MD, Principal investigator		Ph: 301-435-4654 Email: gressr@exchange.nih.gov

U.S.A.
Maryland
	Baltimore
	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
		Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Center at John Hopkins	Ph:  410-955-8804
			Email: jhcccro@jhmi.edu
	Bethesda
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office	Ph:  888-NCI-1937
New Jersey
	Hackensack
	Hackensack University Medical Center Cancer Center
		Clinical Trials Office - Hackensack University Medical Center Cancer Center	Ph:  201-996-2879

Registry Information
Official Title		Multi-Institutional Prospective Phase II Study of Montelukast for the Treatment of Bronchiolitis Obliterans Following Allogeneic Stem Cell Transplantation in Children and Adults
Trial Start Date		2008-02-21
Trial Completion Date		2011-02-21 (estimated)
Registered in ClinicalTrials.gov		NCT00656058
Date Submitted to PDQ		2008-03-28
Information Last Verified		2008-08-13

Back to Top