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
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.
To evaluate if montelukast stabilizes or improves pulmonary function in patients with BO
after BMT using FEV-1 changes as primary endpoints, and oxygen saturation, pulmonary
function test (PFT) parameters (FEF 25-75, RV and RV/FVC, DLC02, FEV-1/FVC, FEV-1/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
To determine if montelukast improves other cGVHD manifestations, quality of life, and
Patients greater than or equal to 6 years old with bronchiolitis obliterans following stem
cell transplantation for any disease indication may be enrolled.
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
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 3 institutions: NIH, Johns Hopkins Hospital, and
Hackensack Hospital. Forty-five patients will be enrolled on this trial.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Comparison of the proportion of patients with stable or improved percentage or predeicted FEV1 with published literature.
Ronald E Gress, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|
|Fred Hutchinson Cancer Research Center||Seattle, Washington 98109|