Montelukast in Treating Patients With Bronchiolitis Obliterans After Donor Stem Cell Transplant - Full Text View

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00656058

Purpose

RATIONALE: Montelukast may be effective in treating bronchiolitis obliterans after donor stem cell transplant.

PURPOSE: This phase II trial is studying how well montelukast works in treating patients with bronchiolitis obliterans after donor stem cell transplant.

Condition	Intervention	Phase
Cancer	Drug: montelukast sodium Procedure: flow cytometry Procedure: laboratory biomarker analysis Procedure: quality-of-life assessment	Phase II

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Hodgkin's Disease Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma Multiple Myeloma

Drug Information available for: Montelukast sodium Montelukast

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Supportive Care, Non-Randomized, Open Label
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Comparison of the proportion of patients with stable or improved percentage of predicted FEV1 with published literature [ Designated as safety issue: No ]
Comparison of the slope of FEV1 before and after treatment with montelukast sodium [ Designated as safety issue: No ]

Secondary Outcome Measures:

Oxygen saturation and supplementation [ Designated as safety issue: No ]
Pulmonary function tests, including FEF25-75, RV or RV/FVC, DLCO2, and the ratio of FEV1/FVC and FEV1/SVC [ Designated as safety issue: No ]
Pulmonary endurance as measured by a 2- and 6-minute walk test [ Designated as safety issue: No ]
Leukotriene levels in the urine and blood and leukotriene receptor expression on activated circulating immune cells [ Designated as safety issue: No ]
Other chronic graft-vs-host disease manifestations [ Designated as safety issue: No ]
Quality of life and function parameters [ Designated as safety issue: No ]
Overall survival at 2 years [ Designated as safety issue: No ]

Estimated Enrollment:	45
Study Start Date:	February 2008
Estimated Primary Completion Date:	February 2011 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

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 FEV_1 in these patients with a benchmark control from publications and by comparing the FEV_1 slope (of the absolute value) before and after treatment with montelukast sodium.

Secondary

To confirm the safety profile of montelukast sodium in these patients.
To determine if montelukast sodium improves oxygen saturation or decreases oxygen requirement in these patients.
To assess if montelukast sodium improves other pulmonary function parameters, including FEF25-75, RV, DLC02, and the ratio of FEV_1/FVC and FEV_1/SVC, in these patients.
To determine if montelukast sodium improves pulmonary endurance in these patients as measured by a 2- and 6-minute walk test.
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.
To determine if improvement in pulmonary function correlates with decreased leukotriene levels or leukotriene receptor expression on activated circulating immune cells.
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.
To evaluate if the introduction of montelukast sodium impacts the 2-year overall survival of these patients.

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.

Eligibility

Ages Eligible for Study:	6 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of bronchiolitis obliterans (BO) following allogeneic stem cell transplantation, meeting all of the following criteria:
- FEV_1 < 75% of predicted by pulmonary function test (PFT) for height and weight
  - Patients must have 2 PFT measurements with documented FEV_1 values > 3 months apart to calculate the FEV_1 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
  - FEV_1/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 FEV_1
- 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 FEV_1 prior to study enrollment
No tumor burden greater than minimal residual disease (i.e., tumor burden that can only be detected by molecular methods)

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%
FEV_1 ≥ 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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00656058

Locations

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Recruiting
Baltimore, Maryland, United States, 21231-2410
Contact: Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce 410-955-8804 jhcccro@jhmi.edu
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center 888-NCI-1937
United States, New Jersey
Hackensack University Medical Center Cancer Center	Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Clinical Trials Office - Hackensack University Medical Center 201-996-2879

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Ronald E. Gress, MD

NCI - Experimental Transplantation and Immunology Branch

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000593080, NCI-08-C-0097, NCI-P07261
Study First Received:	April 9, 2008
Last Updated:	January 9, 2009
ClinicalTrials.gov Identifier:	NCT00656058
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

graft versus host disease
bronchiolitis obliterans
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult Hodgkin lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage III marginal zone lymphoma
stage III small lymphocytic lymphoma

stage IV adult Burkitt lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult Hodgkin lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV mantle cell lymphoma
stage IV marginal zone lymphoma
stage IV small lymphocytic lymphoma
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma

Study placed in the following topic categories:

Juvenile myelomonocytic leukemia
Blast Crisis
Sezary syndrome
Chronic myelogenous leukemia
Chronic myelomonocytic leukemia
Graft versus host disease
Hodgkin lymphoma, adult
Lymphoma, Mantle-Cell
Lymphoma, small cleaved-cell, diffuse
Ovarian epithelial cancer
Small non-cleaved cell lymphoma
Lymphoma, large-cell, immunoblastic
Bronchiolitis Obliterans
Mycoses
Preleukemia

Multiple myeloma
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasm Metastasis
Acute myeloid leukemia, adult
Hodgkin Disease
Rhabdomyosarcoma
Chronic lymphocytic leukemia
Myelodysplastic syndromes
Lung Diseases, Interstitial
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, B-cell, chronic
Leukemia, Myelomonocytic, Chronic
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative

Additional relevant MeSH terms:

Respiratory System Agents
Neoplasms
Neoplasms by Histologic Type
Immune System Diseases
Bronchial Diseases
Therapeutic Uses

Hormone Antagonists
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Asthmatic Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009