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

• Status: Recruiting
• Trial end date: 2022-02-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Basel, Switzerland
• Treatments: Nintedanib

Criteria

Inclusion Criteria:

• Time interval from transplant
• 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