Nintedanib in Patients With Bronchiolitis Obliterans Syndrome Following Hematopoietic Stem Cell Transplantation (NINBOST2018)

University Hospital Basel

Status and phase

Enrolling

Phase 2

Conditions

Bronchiolitis Obliterans Syndrome (BOS)

Bronchiolitis Obliterans (BO)

Treatments

Drug: Nintedanib

Study type

Interventional

Funder types

Other

Identifiers

NCT03805477

2018-00837 me17Hostettler;

Details and patient eligibility

About

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.

Full description

Allogeneic hematopoietic stem cell transplantation (HCT) is an established treatment option for several malignant and non-malignant disorders. An important limitation of long-term survival after HCT is chronic graft-versus-host disease (cGvHD). The manifestation of cGvHD in the lungs, bronchiolitis obliterans (BO - if proven by lung biopsy) or bronchiolitis obliterans syndrome (BOS - clinical diagnosis), has a reported incidence between 5 and 20%. Despite different treatment approaches, prognosis of BO remains poor, with an overall 3-year mortality of up to 65%. Nintedanib is an orally available indolinone derivate that competitively binds to the vascular endothelial growth factor (VEGF) receptors, fibroblast growth factor (FGF) receptors, and platelet derived growth factor (PDGF) receptors. The anti-fibrotic activities of Nintedanib may impact the progressive course of fibrotic lung diseases like BO. This study investigates the safety and tolerability of Nintedanib in patients with bronchiolitis obliterans syndrome following allogeneic hematopoietic cell transplantation.

Enrollment

20 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Time interval from transplant </= 5 years at the time of inclusion
BOS as defined per the National Institute of Health (NIH) criteria:
1. FEV1/vital capacity < 0.7 or the fifth percentile of predicted.
2. FEV1 < 75% of predicted with ≥ 10% decline over less than 2 years.
3. 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).
4. One of the 2 supporting features of BOS: 1. Evidence of air trapping by expiratory CT or small airway thickening or bronchiectasis by high-resolution chest CT, or 2. Evidence of air trapping by PFTs: residual volume > 120% of predicted or residual volume/total lung capacity elevated outside the 90% confidence interval and prior or current diagnosis of cGvHD per NIH criteria or histologically proven BO
Diagnosis of BOS within 6 months before enrollment or prior diagnosis of BOS with an absolute decline of the percentage of predicted forced expiratory volume in 1 second (FEV1) by >/= 10% within the past 12 months before inclusion

Exclusion Criteria

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
Chronic oxygen therapy; non-invasive ventilation
Inability to give informed consent or to perform repeated pulmonary function tests (PFT)
Life expectancy < 1 year at the time of enrolment as suggested by the treating physician
Hematologic malignancy in hematologic relapse
Symptomatic angina pectoris
Therapeutic anticoagulation (primary or secondary prophylactic platelet anti-aggregation allowed)
Recent abdominal surgery or untreated gastric ulcer