Идёт набор NCT03805477

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

Фаза II С лечением Bronchiolitis Obliterans Syndrome (BOS) Bronchiolitis Obliterans (BO)

Ориентир для пациента и семьи

Простыми словами

Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.

Что изучают: В протоколе указаны: Nintedanib.
Кому может быть актуально: Состояния в реестре: Bronchiolitis Obliterans Syndrome (BOS), Bronchiolitis Obliterans (BO). Базовые параметры: от 18 лет · Все.
Что важно проверить: Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
Где проводится: Саудовская Аравия, Швейцария
Следующий шаг: Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →

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Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

Препарат 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

Первичные конечные точки

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

Вторичные конечные точки (12)

change of the percent of predicted forced expiratory volume in 1 second (FEV1) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: Pulmonary function tests will be performed at screening, after 1, 2, 3, 6, 9, 12 and after 13 months]
Nitrogen (N2)-washout [Срок оценки: 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) [Срок оценки: 6-MWD will be performed at screening, after 6, after 12 months]
cumulative steroid doses [Срок оценки: assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months]
occurrence of GvHD in other organs [Срок оценки: assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months]
disease-free survival of underlying hematologic disease [Срок оценки: assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months]
changes in St. George's Respiratory Questionnaire (SGRQ) [Срок оценки: assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months]
changes in NIH GvHD grading score [Срок оценки: assessed at screening, after 1, 2, 3, 6, 9, 12, and after 13 months]

Критерии участия

Критерии включения

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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет