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

NCT ID: NCT03805477

Last Updated: 2025-12-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-20
• Study Completion Date: 2026-12-31

Brief 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.

Detailed 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.

Conditions

Bronchiolitis Obliterans Syndrome (BOS); Bronchiolitis Obliterans (BO)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nintedanib

Nintedanib 150 mg Kps bid (oral)

Group Type: EXPERIMENTAL

Nintedanib

Intervention Type: DRUG

Nintedanib 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

Interventions

Nintedanib

Nintedanib 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

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Katrin Hostettler Haack, PD Dr. med

Role: PRINCIPAL_INVESTIGATOR

Clinic of Respiratory Medicine, University Hospital Basel

Locations

King Faisal Specialist Hospital & Research Centre

Riyadh, , Saudi Arabia

Site Status: RECRUITING

Clinic of Hematology, University Hospital Basel

Basel, , Switzerland

Site Status: RECRUITING

Clinic of Respiratory Medicine, University Hospital Basel

Basel, , Switzerland

Site Status: RECRUITING

Countries

Saudi Arabia; Switzerland

Central Contacts

Katrin Hostettler Haack, PD Dr. med

Role: CONTACT

Katrin.Hostettler@usb.ch

+41 61 328 69 16

Sandra Kunze

Role: CONTACT

Sandra.Kunze@usb.ch

+41 61 328 55 10

Facility Contacts

Marwan Shaheen, MD

Role: primary

Joerg Halter, PD Dr. med

Role: primary

joerg.halter@usb.ch

+41 61 328 65 74

Katrin Hostettler Haack, PD Dr. med

Role: primary

katrin.hostettler@usb.ch

+41 61 328 69 16

Other Identifiers

2018-00837; me17Hostettler

Identifier Type: -

Identifier Source: org_study_id