Исследование эффективности и безопасности руксолитиниба у пациентов с острым синдромом «трансплантат против хозяина», резистентным к стероидам II–IV степени
Одногрупповое многоцентровое исследование руксолитиниба для лечения китайских пациентов с острым заболеванием трансплантата против хозяина II-IV степени, резистентным к кортикостероидам
The purpose of this study is to assess the efficacy and safety of ruxolitinib therapy in Chinese adults and adolescents (≥ 12 years old) with Grade II-IV steroid-refractory acute graft versus host disease (SR-aGvHD).
Обзор исследования
Статус
Вмешательство/лечение
Подробное описание
Participants will start with a screening period to assess the eligibility; only participants who meet all the inclusion and none of the exclusion criteria will start study treatment from Day 1 to Week 24 or end of treatment. Following safety follow up visits, participants will receive the long-term follow-up until Month 12.
Тип исследования
Регистрация (Действительный)
Фаза
- Фаза 4
Контакты и местонахождение
Места учебы
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Beijing, Китай, 100034
- Novartis Investigative Site
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Beijing, Китай, 100070
- Novartis Investigative Site
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Taian, Китай, 271000
- Novartis Investigative Site
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Tianjin, Китай, 300020
- Novartis Investigative Site
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Guangdong
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Guangzhou, Guangdong, Китай, 510515
- Novartis Investigative Site
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Henan
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Zhengzhou, Henan, Китай, 450003
- Novartis Investigative Site
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Hubei
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Wuhan, Hubei, Китай, 430030
- Novartis Investigative Site
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Shanxi
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Xian, Shanxi, Китай, 710061
- Novartis Investigative Site
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Zhejiang
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Hangzhou, Zhejiang, Китай, 310003
- Novartis Investigative Site
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
Key Inclusion criteria
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Male or female Chinese participants aged 12 or older at the time of informed consent. Written informed consent from participant, parent or legal guardian.
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Able to swallow tablets.
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Have undergone alloSCT from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood.
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Clinically diagnosed Grades II to IV acute GvHD as per standard criteria occurring after alloSCT requiring systemic immune suppressive therapy.
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Evident myeloid and platelet engraftment (confirmed within 48 hours prior to study treatment (ruxolitinib) start):
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Confirmed diagnosis of steroid refractory aGvHD defined as participants administered systemic corticosteroids (methylprednisolone at least 1 mg/kg/day [or equivalent prednisone dose at least 1.25 mg/kg/day]), given alone or combined with calcineurin inhibitors (CNI) and either:
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Progression based on organ assessment after at least 3 days compared to organ stage at the time of initiation of systemic corticosteroid +/- CNI for the treatment of Grade II to IV aGvHD. OR
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Failure to achieve at a minimum partial response based on organ assessment after 7 days compared to organ stage at the time of initiation of systemic corticosteroid +/-CNI for the treatment of Grade II to IV. OR
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Participants who fail corticosteroid taper defined as fulfilling either one of the following criteria:
- Requirement for an increase in the corticosteroid dose to methylprednisolone ≥ 1 mg/kg/day (or equivalent prednisone dose ≥ 1.25 mg/kg/day). OR
- Failure to taper the methylprednisolone dose to < 0.5 mg/kg/day (or equivalent prednisone dose <0.6 mg/kg/day) for a minimum of 7 days.
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Key Exclusion criteria
- Has received more than one systemic treatment for steroid refractory aGvHD. Participants who received JAK inhibitor therapy for any indication after initiation of current alloSCT conditioning.
- Clinical presentation resembling de novo chronic GvHD or GvHD overlap syndrome with both acute and chronic GvHD features.
- Failed prior alloSCT within the past 6 months. Presence of relapsed primary malignancy after the alloSCT was performed.
- Presence of an active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment.
- SR-aGvHD occurring after non-scheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. Note: Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible.
- Presence of significant respiratory disease, severely impaired renal function, clinically significant or uncontrolled cardiac disease, unresolved cholestatic and liver disorders (not attributable to aGvHD). Disorders and/or current therapy with medications that interfere with coagulation or platelet function.
Other protocol-defined inclusion / exclusion criteria may apply
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Н/Д
- Интервенционная модель: Одногрупповое задание
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
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Экспериментальный: Ruxolitinib
Participants will receive ruxolitinib orally of 10 mg BID daily (given as two 5-mg tablets, approximately 12 hours apart). |
Ruxolitinib is taken orally daily at 10 mg BID, given as two 5-mg tablets.
Другие имена:
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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Overall Response Rate (ORR) at Day 28 per Investigators
Временное ограничение: Day 28
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The ORR at Day 28 defined as the percentage of participants demonstrating a complete response (CR) or partial response (PR) without requirement for additional systemic therapies for an earlier progression, mixed response or nonresponse, according to standard criteria and assessed by investigators. |
Day 28
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Durable Overall response rate (ORR) at Day 56
Временное ограничение: Day 56
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Durable ORR at Day 56 is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) at Day 28 and maintain a CR or PR at Day 56. |
Day 56
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Duration of Response (DOR)
Временное ограничение: From Week 1 to long term follow up Month 12
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DOR is defined as the time from first response until aGvHD progression or the date of additional systemic therapies for aGvHD. |
From Week 1 to long term follow up Month 12
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Best overall response (BOR)
Временное ограничение: From week 1 to Day 28
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Percentage of participants who achieved overall response (complete response (CR) + Partial response (PR) at any time point up to and including Day 28 and before the start of additional systemic therapy for aGvHD. |
From week 1 to Day 28
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Overall survival (OS)
Временное ограничение: From the date of start of study treatment to date of death, up to approx. 12 months
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Overall survival (OS) is defined as the time from the date of start of study treatment to date of death due to any cause. |
From the date of start of study treatment to date of death, up to approx. 12 months
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Non-relapse mortality (NRM)
Временное ограничение: From date of start of study treatment to date of death, up to approx. 12 months
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Non-relapse mortality (NRM) is defined as the time from date of start of study treatment to date of death not preceded by hematologic disease relapse/progression. |
From date of start of study treatment to date of death, up to approx. 12 months
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Event-free survival (EFS)
Временное ограничение: From the date of start of study treatment to the date of hematologic disease relapse/progression, graft failure, or death, up to approx. 12 months
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Event-free survival (EFS) is defined as the time from the date of start of study treatment to the date of hematologic disease relapse/progression, graft failure, or death due to any cause. |
From the date of start of study treatment to the date of hematologic disease relapse/progression, graft failure, or death, up to approx. 12 months
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Failure-free survival (FFS)
Временное ограничение: From the date of start of study treatment to date of hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGvHD treatment, up to approx. 12 months
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Failure-free survival (FFS) is defined as the time from the date of start of study treatment to date of hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGvHD treatment. |
From the date of start of study treatment to date of hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGvHD treatment, up to approx. 12 months
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Malignancy Relapse/Progression (MR)
Временное ограничение: From date of start of study treatment to hematologic malignancy relapse/progression, up to approx. 12 months
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Malignancy Relapse/Progression (MR) is defined as the time from date of start of study treatment to hematologic malignancy relapse/progression. Calculated for participants with underlying hematologic malignant disease. |
From date of start of study treatment to hematologic malignancy relapse/progression, up to approx. 12 months
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Reduction of daily corticosteroids dose
Временное ограничение: Up to Day 56
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This includes the assessment of systemic corticosteroid use and daily dose, and the percentage of participants successfully tapered off all systemic corticosteroids until Day 56, by time intervals and overall. |
Up to Day 56
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Cumulative incidence of chronic GvHD
Временное ограничение: From Week 1 to long term follow up of month 12
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Cumulative incidence of chronic GvHD (cGvHD) includes mild, moderate and severe occurrences. |
From Week 1 to long term follow up of month 12
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Соавторы и исследователи
Спонсор
Следователи
- Директор по исследованиям: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Первичное завершение (Действительный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
Другие идентификационные номера исследования
- CINC424C2416
Планирование данных отдельных участников (IPD)
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Описание плана IPD
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
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