- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03805477
Nintedanib in Patients With Bronchiolitis Obliterans Syndrome Following Hematopoietic Stem Cell Transplantation (NINBOST2018)
January 31, 2024 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
Recruiting
Intervention / Treatment
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
Interventional
Enrollment (Estimated)
20
Phase
- 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
- Name: Katrin Hostettler Haack, PD Dr. med
- Phone Number: +41 61 328 69 16
- Email: katrin.hostettler@usb.ch
Study Contact Backup
- Name: Sandra Kunze
- Phone Number: +41 61 328 55 10
- Email: Sandra.Kunze@usb.ch
Study Locations
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-
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Riyadh, Saudi Arabia, 11471
- Recruiting
- King Faisal Specialist Hospital & Research Centre
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Contact:
- Marwan Shaheen, MD
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Basel, Switzerland, 4031
- Recruiting
- Clinic of Hematology, University Hospital Basel
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Contact:
- Joerg Halter, PD Dr. med
- Phone Number: +41 61 328 65 74
- Email: joerg.halter@usb.ch
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Basel, Switzerland, 4031
- Recruiting
- Clinic of Respiratory Medicine, University Hospital Basel
-
Contact:
- Katrin Hostettler Haack, PD Dr. med
- Phone Number: +41 61 328 69 16
- Email: katrin.hostettler@usb.ch
-
-
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
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:
- 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
- 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 |
Intervention / Treatment |
---|---|
Experimental: Nintedanib
Nintedanib 150 mg Kps bid (oral)
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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
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
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
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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
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the volume in the lungs at maximal Inflation (measured in liters)
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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
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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.
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6-MWD will be performed at screening, after 6, after 12 months
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cumulative steroid doses
Time Frame: assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months
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steroid doses per month (in mg)
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assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months
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occurrence of GvHD in other organs
Time Frame: assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months
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occurrence of GvHD in other organs
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assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months
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disease-free survival of underlying hematologic disease
Time Frame: assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months
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disease-free survival of underlying hematologic disease
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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.
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assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months
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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)
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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).
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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.
Investigators
- 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)
March 20, 2019
Primary Completion (Estimated)
August 1, 2025
Study Completion (Estimated)
August 1, 2025
Study Registration Dates
First Submitted
January 8, 2019
First Submitted That Met QC Criteria
January 14, 2019
First Posted (Actual)
January 15, 2019
Study Record Updates
Last Update Posted (Actual)
February 1, 2024
Last Update Submitted That Met QC Criteria
January 31, 2024
Last Verified
January 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Immune System Diseases
- Lung Diseases
- Disease
- Bronchial Diseases
- Lung Diseases, Obstructive
- Bronchitis
- Organizing Pneumonia
- Graft vs Host Disease
- Syndrome
- Bronchiolitis
- Bronchiolitis Obliterans
- Bronchiolitis Obliterans Syndrome
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Nintedanib
Other Study ID 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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