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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 February 2024
• Main ID: NCT03805477
• Date of registration: 08/01/2019
• Prospective Registration: Yes
• Primary sponsor: University Hospital, Basel, Switzerland
• Public title: Nintedanib in Patients With Bronchiolitis Obliterans Syndrome Following Hematopoietic Stem Cell Transplantation NINBOST2018
• Scientific title: Nintedanib in Patients With Bronchiolitis Obliterans Syndrome Following Hematopoietic Stem Cell Transplantation (HSCT)- a Multicentre Phase II Trial
• Date of first enrolment: March 20, 2019
• Target sample size: 20
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03805477
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Austria, Germany, Saudi Arabia, Switzerland

Contacts

• Name: Katrin Hostettler Haack, PD Dr. med

• Name: Katrin Hostettler Haack, PD Dr. med
• Affiliation: Clinic of Respiratory Medicine, University Hospital Basel

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Bronchiolitis Obliterans (BO)

Bronchiolitis Obliterans Syndrome (BOS)

Intervention(s)

Drug: Nintedanib

Primary Outcome(s)

adverse event rate leading to interruption/ discontinuation of study treatment [Time Frame: from screening to month 12 after screening]

Secondary Outcome(s)

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 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]

changes in NIH GvHD grading score [Time Frame: 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]

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]

disease-free survival of underlying hematologic disease [Time Frame: assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months]

cumulative steroid doses [Time Frame: 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]

overall survival [Time Frame: 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]

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]

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]

changes in in 6 minutes walking distance (6-MWD) [Time Frame: 6-MWD will be performed at screening, after 6, after 12 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]

Secondary ID(s)

2018-00837; me17Hostettler

Source(s) of Monetary Support

Please refer to primary and secondary sponsors