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

December 5, 2025 updated by: University Hospital, Basel, Switzerland

Nintedanib in Patients With Bronchiolitis Obliterans Syndrome Following Hematopoietic Stem Cell Transplantation (HSCT)- a Multicentre Phase II Trial

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Saudi Arabia
      • Riyadh, Saudi Arabia, 11471
        • Recruiting
        • King Faisal Specialist Hospital & Research Centre
        • Contact:
          • Marwan Shaheen, MD
  • Switzerland
      • Basel, Switzerland, 4031
        • Recruiting
        • Clinic of Hematology, University Hospital Basel
        • Contact:
      • Basel, Switzerland, 4031
        • Recruiting
        • Clinic of Respiratory Medicine, University Hospital Basel
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Nintedanib
Nintedanib 150 mg Kps bid (oral)
Drug: 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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
adverse event rate leading to interruption/ discontinuation of study treatment
Time Frame: from screening to month 12 after screening
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
change of the percent of predicted forced expiratory volume in 1 second (FEV1)
Time Frame: Pulmonary function tests will be performed at screening, after 1, 2, 3, 6, 9, 12 and after 13 months
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
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)
Time Frame: Pulmonary function tests will be performed at screening, after 1, 2, 3, 6, 9, 12 and after 13 months
volume of air that can forcibly be blown out after full inspiration, (measured in Liters)
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)
Time Frame: Pulmonary function tests will be performed at screening, after 1, 2, 3, 6, 9, 12 and after 13 months
the volume in the lungs at maximal Inflation (measured in liters)
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)
Time Frame: Pulmonary function tests will be performed at screening, after 1, 2, 3, 6, 9, 12 and after 13 months
extent to which oxygen passes from the air sacs of the lungs into the blood (measured in "ml/min/kPa)
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)
Time Frame: 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) (measured in parts per Billion)
Pulmonary function tests will be performed at screening, after 1, 2, 3, 6, 9, 12 and after 13 months
Nitrogen (N2)-washout
Time Frame: Pulmonary function tests will be performed at screening, after 1, 2, 3, 6, 9, 12 and after 13 months
The following describes a single-breath nitrogen test: A subject takes a breath of 100% oxygen and exhales through a one-way valve measuring nitrogen content and volume. A plot of the nitrogen concentration (as a % of total gas) vs. expired volume is obtained by increasing the nitrogen concentration from zero to the percentage of nitrogen in the alveoli. The nitrogen concentration is initially zero because the subject is exhaling the dead space oxygen they just breathed in (does not participate in alveolar exchange), and climbs as alveolar air mixes with the dead space air. The dead space can be determined from this curve by drawing a vertical line down the curve such that the areas below the curve (left of the line) and above the curve (right of the line) are equal
Pulmonary function tests will be performed at screening, after 1, 2, 3, 6, 9, 12 and after 13 months
changes in in 6 minutes walking distance (6-MWD)
Time Frame: 6-MWD will be performed at screening, after 6, after 12 months
standardized 6-minute walk test will be performed breathing room air and performed according to the guidelines of the American Thoracic Society. Significant drop of transcutaneous measured arterial oxygen Saturation (SaO2) is defined as a ΔSaO2 ≥ 4% or SaO2 < 90%. A significant change in walking distance will be Δ distance = 40 metre.
6-MWD will be performed at screening, after 6, after 12 months
cumulative steroid doses
Time Frame: assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months
steroid doses per month (in mg)
assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months
occurrence of GvHD in other organs
Time Frame: assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months
occurrence of GvHD in other organs
assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months
disease-free survival of underlying hematologic disease
Time Frame: assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months
disease-free survival of underlying hematologic disease
assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months
changes in St. George's Respiratory Questionnaire (SGRQ)
Time Frame: assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months
The SGRQ is designed to measure health impairment in patients with asthma and chronic obstructive pulmonary disease (COPD); 3 component scores are calculated: symptoms; activity; impacts. Each questionnaire response has a unique empirically derived 'weight'. The lowest possible weight is zero and the highest is 100.
assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months
changes in NIH GvHD grading score
Time Frame: assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months
NIH symptom-based lung score (score 0: no symptoms, score 1: shortness of breath with stairs, score 2: shortness of breath on flat ground, score 3: shortness of breath at rest or requiring oxygen)
assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months
changes in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) questionnaire
Time Frame: assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months
specific HSCT-patients validated self-report questionnaire using a 5 point Likert scale and covering 4 specific domains that include physical, social and family, emotional and functional well-being. Scoring produces a range from 0-148, the higher the score, the better the Quality of Life (QOL).
assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months
overall survival
Time Frame: assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months
overall survival
assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Basel, Switzerland

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Katrin Hostettler Haack, PD Dr. med, Clinic of Respiratory Medicine, University Hospital Basel

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 20, 2019

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 8, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 14, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 15, 2019

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 15, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 5, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2018-00837; me17Hostettler

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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