This study investigates the safety and tolerability of Nintedanib in patients with bronchiolitis obliterans syndrome (BOS) following allogeneic hematopoietic cell transplantation. All study patients with BOS will be treated with the study drug Nintedanib (300 mg/day) as an add-on therapy to their basic immunosuppressive treatment over a 12-months treatment period.
Time interval from transplant </= 5 years at the time of inclusion
FEV1/vital capacity < 0.7 or the fifth percentile of predicted.
FEV1 < 75% of predicted with ≥ 10% decline over less than 2 years.
Absence of infection in the respiratory tract, documented with investigations directed by clinical symptoms, such as chest radiographs, computed tomographic (CT) scans, or microbiologic cultures (sinus aspiration, upper respiratory tract viral screen, sputum culture, and broncho-alveolar lavage).
Known intolerance to Nintedanib or any of its component
Pregnancy or nursing
Serum ALT > 5 x upper limit of normal (ULN) unless explained entirely by liver GvHD or total bilirubin > 3x ULN unless explained entirely by liver GvHD
Any acute pulmonary infection with viruses, bacteria or fungi within four weeks before study inclusion
Single group
Nintedanib
DrugNintedanib 150 mg Kps bid (oral); in order to manage adverse events, the dose of Nintedanib may be reduced from 150 mg twice daily to 100 mg twice daily
adverse event rate leading to interruption/ discontinuation of study treatment
adverse events of the following severity according to Common terminology criteria for adverse events(CTCAE): Diarrhoea ≥ grade 3; Nausea ≥ grade 3; Vomiting ≥ grade 3; Abdominal pain ≥ grade 3; Elevation of liver enzymes (AST, ALT) ≥ grade 2; Elevation of total bilirubin ≥ 2
change of the percent of predicted forced expiratory volume in 1 second (FEV1)
absolute change of the percent of predicted FEV1 by ≥10% from FEV1 before enrolment (eg, 50% to 40% predicted FEV1), confirmed by 2 pulmonary function tests (PFT) performed at least two weeks apart and after exclusion of infections and extra pulmonary causes
change in forced vital capacity (FVC)
volume of air that can forcibly be blown out after full inspiration, (measured in Liters)
change in total lung capacity (TLC)
the volume in the lungs at maximal Inflation (measured in liters)
Change in diffusion capacity of the lung for carbon monoxide (DLCO)
extent to which oxygen passes from the air sacs of the lungs into the blood (measured in "ml/min/kPa)
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