The Safety and Efficacy of BRL-201 in the Treatment of r/r B Lymphocyte Non-Hodgkin Lymphoma

Официальное название

A Phase I/II Clinical Study of the Safety and Efficacy of CD19-targeted Non-viral PD1 Site-specific Integrated CAR-T Cell Injection (BRL-201) in the Treatment of Relapsed or Refractory B Lymphocyte Non-Hodgkin Lymphoma

Обзор

This is a multi-center, single-arm, open-label clinical study, and the sample size is set to 12-18 subjects.

Подробное описание

This is a multi-center, single-arm, open-label clinical study, and the sample size is set to 12-18 subjects. Based on the "3 + 3" dose escalation design principle, subjects will be divided into 3 groups from low dose to high dose in sequence (Group A; Group B; Group C. Additional subjects will be enrolled into the RP2D group to ensure that 6-9 efficacy-evaluable subjects are available in the RP2D group before entering the phase II study.

Вмешательства

• Препарат CD19-targeted non-viral PD1 site-specific integrated CAR-T cell injection
  CD19-targeted non-viral PD1 site-specific integrated CAR-T cell injection

Первичные конечные точки

• DLT [Срок оценки: Within 28 Days After BRL-201 Infusion]
• AEs [Срок оценки: Up to 24 Months After BRL-201 Infusion]
• RP2D [Срок оценки: Within 28 Days After BRL-201 Infusion]

Критерии участия

Критерии включения

• Willing to participate in this clinical study and sign an informed consent form;
• Age ≥ 18 years old;
• Estimated survival time ≥ 3 months;
• Presence of at least one measurable lesion as assessed according to Lugano Classification 2014 for response assessment in lymphomas (i.e., the cross-sectional images obtained by CT show that the long diameter of lymph node lesions is > 15 mm or the long diameter of extranodal lesions is > 10 mm, and FDG-PET scan results are positive). Lesions, for which radiotherapy was provided, can be regarded as measurable lesions only if there is an unequivocal progression after radiotherapy;
• Histopathologically confirmed aggressive B-NHL; positive expression of CD19 in tumors detected by immunohistochemistry or flow cytometry; pathological types of B-NHL (according to WHO Lymphoma Classification 2016);
• Relapsed or refractory diseases;
• Subjects who must receive adequate prior therapy;
• Absence of invasion of central nervous system (CNS) lymphoma by cranial magnetic resonance imaging (MRI);
• Hematological parameters meeting the requirements;
• Blood biochemistry meeting the requirements;
• LVEF ≥ 55%;
• No severe pulmonary disorders;
• Toxic reactions induced by prior anti-lymphoma therapy must be stable and resolved to grade ≤ 1;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
• Patients with physical conditions for apheresis of peripheral blood; 16 . Willing to abide by the rules formulated in the study protocol.

Критерии исключения

• Pregnant or lactating women;
• Subjects who previously received allogeneic cell therapies, including allogeneic stem cell transplant;
• Subjects who previously received anti-CD19 targeted therapy, except those who receive BRL-201 and are eligible to receive reinfusion in this study;
• Prior treatment with any CAR-T cell product or other genetically modified T cell therapies;
• History of Richter's transformation of chronic lymphocytic leukemia (CLL);
• Presence of uncontrollable fungal, bacterial, viral, or other infections requiring systemic therapy. Patients can be enrolled if the simple urinary tract infection or pharyngitis responds to treatment;
• Subjects with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and peripheral blood HBV DNA titer higher than the upper limit of detection; hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive; human immunodeficiency virus (HIV) antibody positive; syphilis test positive;
• Severe mental disorders; history of CNS disorders (e.g., epileptic seizure, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases, or any CNS-involved autoimmune disorders);
• Active autoimmune disorders requiring immunotherapy, including but not limited to end organ damages caused by autoimmune disorders (e.g., Crohn's disease, rheumatoid arthritis, and systemic lupus erythematosus) in the past 2 years, or requiring systemic application of immunosuppressive drugs or other drugs for systemic control of diseases;
• Primary immunodeficiency;
• History of other malignancies;
• Patients with severe cardiovascular disorders, including but not limited to those with lymphoma infiltration in the cardiac atrium or ventricles and those with a history of myocardial infarction, cardioangioplasty or stent implantation, unstable angina, or other clinically significant heart diseases within 12 months before enrollment;
• History of deep venous thrombosis or pulmonary embolism within 6 months before enrollment;
• Patients who are receiving oral anticoagulant therapy; prothrombin time (PT), activated partial thromboplastin time (APTT), or international normalized ratio (INR) > 1.5 × ULN without anticoagulant therapy;
• Presence of any indwelling tube or catheter (e.g., tube or catheter for percutaneous nephrostomy, indwelling catheter, or catheter in pleural cavity/peritoneal cavity/pericardium). Dedicated central venous access catheters (e.g., Port-a-Cath or Hickman catheter) are permitted;
• Lymphoma cells detected in cerebrospinal fluid, presence of brain metastases, history of CNS lymphoma, or history of lymphoma cells detected in cerebrospinal fluid or brain metastases;
• Conditions (e.g., intestinal obstruction or vascular compression) requiring emergency treatment due to tumor masses;
• History of severe immediate hypersensitivity to any drug to be used in this study;
• Vaccination of live vaccines, excluding corona virus disease 2019 (COVID-19) vaccines, within ≤ 6 weeks before the start of the pretreatment regimen;
• Any circumstances that possibly increase the risk of subjects or interfere with the study results as judged by the investigator.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 3 центра

• Wuhan Union Hospital — Ухань
• Tianjin Institute of Hematology — Тяньцзинь
• The First Affiliated Hospital of Zhejiang University — Ханчжоу

Идентификаторы

NCT: NCT05741359 · 2022-BRL-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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