Исследование HMPL-760 Puls R-GemOx в сравнении с плацебо плюс R-GemOx при рецидивирующем/рефрактерном DLBCL
Рандомизированное контролируемое исследование фазы II для оценки эффективности, безопасности и фармакокинетики HMPL-760 плюс R-GemOx по сравнению с плацебо плюс R-GemOx у пациентов с рецидивирующей/рефрактерной диффузной крупноклеточной B-клеточной лимфомой (R/R DLBCL)
The goal of this study is to evaluate the efficacy of HMPL-760 in combination with R-GemOx versus placebo in combination with R-GemOx in patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL).
Обзор исследования
Статус
Подробное описание
A Phase II Randomized, Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of HMPL-760 in Combination with R-GemOx versus Placebo in Combination with R-GemOx in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL). The study phases include screening period, treatment period, safety observation period, PFS follow-up period, and OS follow-up period.
Тип исследования
Регистрация (Действительный)
Фаза
- Фаза 2
Контакты и местонахождение
Места учебы
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Fujian
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Fuzhou, Fujian, Китай
- Fujian Medical University Union Hospital
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Guangdong
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Guangzhou, Guangdong, Китай
- Sun Yat-sen University Cancer Center
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Guangxi
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Nanning, Guangxi, Китай
- Guangxi Medical University Cancer Hospital
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Hebei
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Wuhan, Hebei, Китай
- Wuhan Union Hospital of China
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Heilongjiang
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Harbin, Heilongjiang, Китай
- Harbin Medical University Cancer Hospital
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Harbin, Heilongjiang, Китай
- Harbin First Hospital
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Henan
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Zhengzhou, Henan, Китай
- Henan Cancer Hospital
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Zhengzhou, Henan, Китай
- The First Affiliated Hospital of Zhengzhou University
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Hunan
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Changsha, Hunan, Китай
- Hunan Cancer Hospital
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Jiangxi
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Nanchang, Jiangxi, Китай
- Jiangxi Cancer Hospital
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Nanchang, Jiangxi, Китай
- The First Affiliated Hospital of Nanchang University
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Liaoning
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Shenyang, Liaoning, Китай
- Shengjing Hospital of China Medical University
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Shandong
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Jinan, Shandong, Китай
- Shandong Cancer Hospital & Institute
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Shanghai Municipality
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Shanghai, Shanghai Municipality, Китай
- Ruijin Hospital, Shanghai Jiaotong University School of Medicine
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Sichuan
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Chengdu, Sichuan, Китай
- West China Hospital of Sichuan University
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Tianjin Municipality
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Tianjin, Tianjin Municipality, Китай
- Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
Inclusion Criteria:
- Sign the Informed consent form(ICF) and be able to follow the requirements of study protocol;
- Age ≥18 years;
- Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2;
- Histopathologically confirmed diagnosis of DLBCL;
- The investigator judges that the patient's current condition requires further treatment;
- Patients should have at least one bi-dimensionally measurable lesion;
- Expected survival is more than 12 weeks;
Exclusion Criteria:
- Patients with known primary or secondary central nervous system lymphoma (CNSL) or the presence of clinical symptoms suggestive of CNSL;
- Women who are pregnant (positive pregnancy test during the screening period) or breastfeeding;
- Organ insufficiency;
- Currently known history of liver disease, including cirrhosis, alcoholic liver, known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV):
- History of significant organ bleeding, including gastrointestinal bleeding, hematencephalon, haemoptysis, etc., within 8 weeks prior to the first dose of study drug;
- Known risk of bleeding, such as coagulation factor deficiency, vascular hemophilia; or the patient is receiving vitamin K antagonist (warfarin);
- Toxicities from prior anticancer therapy not resolved to Grade ≤ 1 (except for alopecia and decreased appetite);
- Clinically significant active infection;
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Рандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Четырехместный
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
|
Экспериментальный: Group A: HMPL-760 planned dose 1 once daily (QD) in combination with R-GemOx regimen
Group A: Patients will receive HMPL-760 planned dose 1 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle. |
HMPL-760 planned dose 1 daily (QD) orally R-GemOx regimen includes Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection. R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
Другие имена:
|
|
Плацебо Компаратор: Group B: HMPL-760 placebo planned dose 1 once daily (QD) in combination with R-GemOx regimen
Patients will receive HMPL-760 placebo planned dose 1 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle. |
R-GemOx regimen includes Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection. R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
Другие имена:
HMPL-760 placebo planned dose 1 daily (QD) orally |
|
Экспериментальный: Group C: HMPL-760 planned dose 2 once daily (QD) in combination with R-GemOx regimen
Patients will receive HMPL-760 planned dose 2 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle. |
R-GemOx regimen includes Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection. R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
Другие имена:
HMPL-760 planned dose 2 daily (QD) orally |
|
Плацебо Компаратор: Group D: HMPL-760 placebo planned dose 2 once daily (QD) in combination with R-GemOx regimen
Patients will receive HMPL-760 placebo planned dose 2 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle. |
R-GemOx regimen includes Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection. R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
Другие имена:
HMPL-760 placebo planned dose 2 daily (QD) orally |
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Progression-free survival (PFS)
Временное ограничение: Up to approximately 2 years
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Progression-free survival (PFS): Efficacy is evaluated using the Lugano Efficacy Evaluation Criteria for Malignant Lymphoma (Cheson 2014). |
Up to approximately 2 years
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Objective Response Rate (ORR)
Временное ограничение: Up to approximately 2 years
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Objective Response Rate (ORR) is defined as the ratio of patients who reached complete response (CR) or partial response (PR), as assessed by investigator. |
Up to approximately 2 years
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Complete response (CR) rate
Временное ограничение: Up to approximately 2 years
|
Complete response (CR) rate is defined as the ratio of patients with who reached complete response (CR), as assessed by investigator. |
Up to approximately 2 years
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Duration of response (DoR)
Временное ограничение: Up to approximately 2 years
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For patients who reached complete response (CR) or partial response (PR), Duration of Response (DoR) is defined as the time from the first CR or PR until disease progression or death due to any cause, whichever occurs first, as assessed by investigator. |
Up to approximately 2 years
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Clinical benefit rate (CBR)
Временное ограничение: Up to approximately 2 years
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Defined as the ratio of patients with complete response (CR), partial response (PR), or stable disease (SD). |
Up to approximately 2 years
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Time to response (TTR)
Временное ограничение: Up to approximately 2 years
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Time To Response (TTR) is defined as the time from the start of treatment to the first objective response rate (ORR), as assessed by investigator. |
Up to approximately 2 years
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|
Overall survival (OS)
Временное ограничение: Up to approximately 2 years
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Overall Survival (OS) is defined as the time from randomization to death due to any cause. |
Up to approximately 2 years
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Safety Endpoints of adverse events
Временное ограничение: Up to approximately 2 years
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Incidence and severity of treatment-emergent adverse events (TEAEs), incidence of serious adverse events (SAEs), incidence of TEAEs leading to permanent discontinuation, dose interruption, and dose reduction, and their correlation to study drug. The severity is determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE 5.0). |
Up to approximately 2 years
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Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Временное ограничение: At the end of Cycle 7 (each cycle is 21 days)
|
Trough plasma concentration (Ctrough) of drug |
At the end of Cycle 7 (each cycle is 21 days)
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Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Временное ограничение: At the end of Cycle 7 (each cycle is 21 days)
|
Maximum observed concentration, occurring at time Tmax at steady-state (Cmax,ss) of drug |
At the end of Cycle 7 (each cycle is 21 days)
|
|
Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Временное ограничение: At the end of Cycle 7 (each cycle is 21 days)
|
Time of maximum observed concentration at steady-state(Tmax,ss) of drug |
At the end of Cycle 7 (each cycle is 21 days)
|
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Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Временное ограничение: At the end of Cycle 7 (each cycle is 21 days)
|
The partial area from dosing time to dosing time plus Tau at steady-state (AUCss) of drug |
At the end of Cycle 7 (each cycle is 21 days)
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Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Временное ограничение: At the end of Cycle 7 (each cycle is 21 days)
|
Apparent clearance at steady-state (CLss/F) of drug (if applicable) |
At the end of Cycle 7 (each cycle is 21 days)
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Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Временное ограничение: At the end of Cycle 7 (each cycle is 21 days)
|
Apparent volume of distribution at steady-state (Vz,ss/F) of drug (if applicable) |
At the end of Cycle 7 (each cycle is 21 days)
|
Другие показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Biomarker assessment
Временное ограничение: Up to approximately 2 years
|
To evaluate the correlation between potential biomarkers and the prognosis of patients treated with this regimen. Tumor tissue or blood samples will be examined to detect the gene expression of MYD88. |
Up to approximately 2 years
|
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Metabolite analysis of HMPL-760 in combination with R-GemOx
Временное ограничение: At the end of Cycle 7 (each cycle is 21 days)
|
Analysis metabolite of HMPL-760 in combination with R-GemOx |
At the end of Cycle 7 (each cycle is 21 days)
|
Соавторы и исследователи
Спонсор
Следователи
- Главный следователь: Weili Zhao, Ruijin Hospital
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Первичное завершение (Действительный)
Завершение исследования (Действительный)
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
Дополнительные соответствующие термины MeSH
- Новообразования
- Заболевания иммунной системы
- Новообразования по гистологическому типу
- Лимфатические заболевания
- Лимфопролиферативные заболевания
- Иммунопролиферативные заболевания
- Лимфома, неходжкинская
- Лимфома, В-клеточная
- Лимфома
- Гемики и лимфатические заболевания
- Лимфома, крупная В-клеточная, диффузная
- Аминокислоты, пептиды и белки
- Белки
- Гетероциклические соединения, 1-кольцо
- Гетероциклические соединения
- Терапия
- Маршруты Управления лекарств
- Лекарственная терапия
- Антитела, моноклональные
- Антитела
- Иммуноглобулины
- Иммунопротеины
- Белки крови
- Сывороточные глобулины
- Глобулины
- Дезоксицитидин
- Цитидин
- Пиримидиновые нуклеозиды
- Пиримидины
- Антитела, моноклональные, происходящие из мыши
- Ритуксимаб
- Гемцитабин
- Инъекции
Другие идентификационные номера исследования
- 2024-760-00CH1
Планирование данных отдельных участников (IPD)
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