Multi-target Drugs Sequential Combination Therapy in Adults Patients With Newly Diagnosed Primary Immune Thrombocytopenia
Efficacy and Safety of Multi-Target Drugs Sequential Combination Therapy in Adults Patients With Newly Diagnosed Primary Immune Thrombocytopenia: A Prospective, Single-arm, Multicenter, Exploratory Trial
This prospective, single-arm, multicenter, exploratory study will enroll 38 adults patients with newly diagnosed primary immune thrombocytopenia (ITP). Patients will receive standard-dose corticosteroids plus a thrombopoietin receptor agonist (TPO-RA) as initial therapy During the core treatment phase (Weeks 1-12). Corticosteroids will be tapered and discontinued within 8 weeks, whereas TPO-RA treatment will continue for 12 weeks. For patients with treatment failure( defined as platelet count < 30 × 10^9/L or less than 2-fold increase of baseline platelet count or bleeding) ,a sequential multitarget combination strategy will be explored in subsequent treatment phases. Specifically, patients with treatment failure after 2 weeks of initial therapy (Weeks 3-12), will receive the ongoing TPO-RA in combination with either rituximab or an anti-CD38 monoclonal antibody（mAb） as sequential combination therapy.
During the core treatment follow-up phase (24 weeks), patients with treatment failure will enter the exploratory treatment phase (Weeks 13-36) .
Patients who received multi-target drug therapy during the core treatment period will switch to an alternative TPO-RA with cross-administered rituximab and anti-CD38 mAb, while those who did not will receive sequential rituximab or anti-CD38 mAb.
Finally, patients will enter the safety follow up period (4 weeks, weeks 37-40).
Обзор исследования
Статус
Условия
Подробное описание
The study will be conducted in three phases.
Phase 1. Core treatment phase includes initial treatment and sequential combination therapy (12 weeks, weeks 1-12):
Patients will receive standard-dose methylprednisolone or prednisone in combination with a thrombopoietin receptor agonist (TPO-RA) as initial therapy.Corticosteroids will be tapered and discontinued within 8 weeks; tapering will begin immediately in patients who achieve complete response (CR) and will also be initiated after 4 weeks in patients who do not achieve response (R). TPO-RA therapy will continue for 12 weeks, with dose adjustments made according to the approved prescribing information. Patients with treatment failure( defined as platelet count < 30 × 10^9/L or less than 2-fold increase of baseline platelet count or bleeding) after 2 weeks of initial therapy (Weeks 3-12) will receive the ongoing TPO-RA in combination with either rituximab or an anti-CD38 monoclonal antibody as sequential combination therapy.
Phase 2. Core-treatment follow-up and exploratory treatment phase (24weeks, weeks 13-36):
During the core treatment follow-up phase, patients with treatment failure will enter the exploratory treatment phase. Patients who did not receive rituximab or anti-CD38 monoclonal antibody during the core treatment phase will receive a switched TPO-RA combined with either rituximab or anti-CD38 monoclonal antibody, whereas patients who received either rituximab or anti-CD38 monoclonal antibody during the core phase will receive a switched TPO-RA combined with cross-administered rituximab and anti-CD38 monoclonal antibody.TPO-RA therapy will also continue for 12 weeks.
Phase3. Safety follow-up phase (4weeks,weeks 37-40).
Rescue therapy includes, but is not limited to, intravenous immunoglobulin (IVIG), platelet transfusion, and vindesine. A switch to another thrombopoietin receptor agonist (TPO-RA) will be considered rescue therapy during the core treatment period. Administration of recombinant human thrombopoietin (rhTPO) will also be considered rescue therapy.
Тип исследования
Регистрация (Оцененный)
Фаза
- Фаза 4
Контакты и местонахождение
Контакты исследования
- Имя: Xiaofan Liu
- Номер телефона: +86-022-23608180
- Электронная почта: liuxiaofan@ihcams.ac.cn
Учебное резервное копирование контактов
- Имя: Rongfeng Fu
- Электронная почта: furongfeng@ihcams.ac.cn
Места учебы
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Tianjin, Китай, 300020
- Рекрутинг
- Ethics Committee of Hematology Hospital, Chinese Academy of Medical Sciences
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Контакт:
- Shuo Chen
- Номер телефона: +86-022-23608025
- Электронная почта: ec@ihcams.ac.cn
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
- Взрослый
- Пожилой взрослый
Принимает здоровых добровольцев
Описание
Inclusion Criteria:
- Age ≥18 years.
- Confirmed newly diagnosed primary ITP with a platelet count <30 × 10^9/L.
- No prior ITP-related treatment before enrollment, except for standard-dose corticosteroids and/or IVIG for ≤5 days.
- Able to understand the study and provide signed informed consent.-
Exclusion Criteria:
- Use of corticosteroids or immunosuppressants for a non-ITP condition within 3 months.
- Contraindication to corticosteroid therapy.
- Arterial or venous thromboembolic event within 3 months.
- Pregnant or breastfeeding women.
- Current treatment with another investigational drug.
Any other medical history or condition that, in the investigator's judgment, makes the participant unsuitable for the study.
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Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Нерандомизированный
- Интервенционная модель: Последовательное назначение
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
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Экспериментальный: Initial therapy
standard-dose corticosteroids plus a thrombopoietin receptor agonist (TPO-RA)
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Methylprednisolone 0.8-1mg/kg/day administered intravenously or orally; or prednisone 1 mg/kg/day, up to a maximum dose of 80 mg/day
Dosing will follow the recommended dose in the prescribing information; in severe ITP, the initial dose will be selected according to BAT (best available therapy) principles.
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Экспериментальный: Sequential Combination Therapy
the ongoing TPO-RA in combination with either rituximab or an anti-CD38 monoclonal antibody（mAb）
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Dosing will follow the recommended dose in the prescribing information; in severe ITP, the initial dose will be selected according to BAT (best available therapy) principles.
Administered as 375 mg/m² by intravenous infusion for a single dose, or 100 mg by intravenous infusion once weekly for a total of 4 doses.
Administered at 16 mg/kg by intravenous infusion once weekly for a total of 4-8 doses.
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Экспериментальный: Exploratory treatment
a switched TPO-RA combined with either rituximab or anti-CD38 monoclonal antibody
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Dosing will follow the recommended dose in the prescribing information; in severe ITP, the initial dose will be selected according to BAT (best available therapy) principles.
Administered as 375 mg/m² by intravenous infusion for a single dose, or 100 mg by intravenous infusion once weekly for a total of 4 doses.
Administered at 16 mg/kg by intravenous infusion once weekly for a total of 4-8 doses.
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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
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sustained response rate
Временное ограничение: between weeks 13 and 36
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Defined as the proportion of patients who achieve a platelet count ≥30×10^9/L at least 6 out of 12 scheduled visits during the 24 weeks following the core treatment period (weeks 13-36), in the absence of rescue therapy
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between weeks 13 and 36
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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time to response
Временное ограничение: in 0-12 weeks
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The time from treatment initiation to achieve a complete response(platelet count ≥100 × 109/L and absence of bleeding) or a partial response(platelet count ≥30 × 10^9/L and at least 2-fold increase of the baseline platelet count and absence of bleeding)
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in 0-12 weeks
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Early response.
Временное ограничение: at 1 week
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Proportion of patients achieving platelet count ≥30 × 10^9/L and at least doubling baseline at 1 week after treatment initiation.
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at 1 week
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Initial response
Временное ограничение: at 1 month
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Proportion of patients achieving platelet count ≥30 × 10^9/L and at least doubling baseline at 1 month after treatment initiation.
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at 1 month
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overall response(OR) rate at week 12
Временное ограничение: at week 12
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Proportion of patients achieving complete response (CR) plus response (R) at Week 12
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at week 12
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Proportion of patients requiring rescue therapy
Временное ограничение: in 0-36 weeks
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in 0-36 weeks
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bleeding scores
Временное ограничение: in 0-40 weeks
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Assessed according to the WHO Bleeding Scale and the ITP Bleeding Scale
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in 0-40 weeks
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Immune Thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ)
Временное ограничение: in 0-40 weeks
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In all participants ,use ITP-PAQ to assess the HRQoL before and after treatment.
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in 0-40 weeks
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Functional Assessment of 36-Item Short Form Survey (SF-36) scale
Временное ограничение: in 0-40 weeks
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In all participants ,use SF-36 scale to assess the HRQoL before and after treatment.
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in 0-40 weeks
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Соавторы и исследователи
Следователи
- Директор по исследованиям: Lei Zhang, Thrombosis and Haemostasis Diagnosis Treatment Center
Публикации и полезные ссылки
Общие публикации
- Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N, Godeau B, Lechner K, Mazzucconi MG, McMillan R, Sanz MA, Imbach P, Blanchette V, Kuhne T, Ruggeri M, George JN. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009 Mar 12;113(11):2386-93. doi: 10.1182/blood-2008-07-162503. Epub 2008 Nov 12.
- Gudbrandsdottir S, Birgens HS, Frederiksen H, Jensen BA, Jensen MK, Kjeldsen L, Klausen TW, Larsen H, Mourits-Andersen HT, Nielsen CH, Nielsen OJ, Plesner T, Pulczynski S, Rasmussen IH, Ronnov-Jessen D, Hasselbalch HC. Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia. Blood. 2013 Mar 14;121(11):1976-81. doi: 10.1182/blood-2012-09-455691. Epub 2013 Jan 4.
- Provan D, Arnold DM, Bussel JB, Chong BH, Cooper N, Gernsheimer T, Ghanima W, Godeau B, Gonzalez-Lopez TJ, Grainger J, Hou M, Kruse C, McDonald V, Michel M, Newland AC, Pavord S, Rodeghiero F, Scully M, Tomiyama Y, Wong RS, Zaja F, Kuter DJ. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019 Nov 26;3(22):3780-3817. doi: 10.1182/bloodadvances.2019000812.
- Neunert C, Terrell DR, Arnold DM, Buchanan G, Cines DB, Cooper N, Cuker A, Despotovic JM, George JN, Grace RF, Kuhne T, Kuter DJ, Lim W, McCrae KR, Pruitt B, Shimanek H, Vesely SK. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019 Dec 10;3(23):3829-3866. doi: 10.1182/bloodadvances.2019000966.
- Chen Y, Xu Y, Li H, Sun T, Cao X, Wang Y, Xue F, Liu W, Liu X, Dong H, Fu R, Dai X, Wang W, Ma Y, Song Z, Chi Y, Ju M, Gu W, Pei X, Yang R, Zhang L. A Novel Anti-CD38 Monoclonal Antibody for Treating Immune Thrombocytopenia. N Engl J Med. 2024 Jun 20;390(23):2178-2190. doi: 10.1056/NEJMoa2400409.
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Первичное завершение (Оцененный)
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
- Цитопения
- Патологические процессы
- Аутоиммунные заболевания
- Заболевания иммунной системы
- Кровотечение
- Кожные проявления
- Гематологические заболевания
- Нарушения свертывания крови
- Геморрагические расстройства
- Заболевания тромбоцитов крови
- Тромботические микроангиопатии
- Пурпура, тромбоцитопеническая
- Пурпура
- Тромбоцитопения
- Патологические состояния, признаки и симптомы
- Признаки и симптомы
- Гемики и лимфатические заболевания
- Пурпура, тромбоцитопеническая, идиопатическая
- Аминокислоты, пептиды и белки
- Белки
- Полициклические соединения
- Антитела, моноклональные
- Антитела
- Иммуноглобулины
- Иммунопротеины
- Белки крови
- Сывороточные глобулины
- Глобулины
- Беременные
- Беременные
- Стероиды
- Соединения слитого кольца
- Bergyadienetriols
- Беременные
- Антитела, моноклональные, происходящие из мыши
- Преднизолон
- Ритуксимаб
- Преднизолон
- Метилпреднизолон
- Эльтромбопаг
- даратумумаб
Другие идентификационные номера исследования
- IIT2025106
- Investigator-Initiated Trial (Другой номер гранта/финансирования: Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences)
Планирование данных отдельных участников (IPD)
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Описание плана IPD
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.
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .