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

NCT03805477 | Recruiting Phase 2

• 1 other identifier: 2018-00837; me17Hostettler
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 3

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.

Conditions

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

Keywords

allogeneic hematopoietic cell transplantation.; chronic graft-versus-host disease (cGvHD); Nintedanib; fibrotic lung disease

Outcome Measures

Primary Outcomes (1)

• 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

  from screening to month 12 after screening

Secondary Outcomes (14)

• change of the percent of predicted forced expiratory volume in 1 second (FEV1)

  Pulmonary function tests will be performed at screening, after 1, 2, 3, 6, 9, 12 and after 13 months

• change in forced vital capacity (FVC)

  Pulmonary function tests will be performed at screening, after 1, 2, 3, 6, 9, 12 and after 13 months

• change in total lung capacity (TLC)

  Pulmonary function tests will be performed at screening, after 1, 2, 3, 6, 9, 12 and after 13 months

• Change in diffusion capacity of the lung for carbon monoxide (DLCO)

  Pulmonary function tests will be performed at screening, after 1, 2, 3, 6, 9, 12 and after 13 months

• Change in exhaled nitric oxide (eNO)

  Pulmonary function tests will be performed at screening, after 1, 2, 3, 6, 9, 12 and after 13 months

Study Arms (1)

Nintedanib

EXPERIMENTAL

Nintedanib 150 mg Kps bid (oral)

Drug: Nintedanib

Interventions

Nintedanib 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

Nintedanib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BOS as defined per the National Institute of Health (NIH) criteria:
• 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).
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (3)

King Faisal Specialist Hospital & Research Centre

Riyadh, 11471, Saudi Arabia

RECRUITING

Clinic of Hematology, University Hospital Basel

Basel, 4031, Switzerland

RECRUITING

Clinic of Respiratory Medicine, University Hospital Basel

Basel, 4031, Switzerland

RECRUITING

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome; Bronchiolitis Obliterans

Interventions

nintedanib

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Study Officials

• Katrin Hostettler Haack, PD Dr. med

  Clinic of Respiratory Medicine, University Hospital Basel

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katrin Hostettler Haack, PD Dr. med

CONTACT

+41 61 328 69 16; Katrin.Hostettler@usb.ch

Sandra Kunze

CONTACT

+41 61 328 55 10; Sandra.Kunze@usb.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2019
• First Posted: January 15, 2019
• Study Start: March 20, 2019
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 15, 2025

Record last verified: 2025-12

Locations

SA (1); CH (2)