Efficacy and Safety of CD19CD20-CAR.p40-T in B-cell Lymphoma

Официальное название

Study on the Efficacy and Safety of Autocrine p40 Chimeric Antigen Receptor T Cells Targeting CD19 and CD20 (CD19CD20-CAR.p40-T) in Refractory B-Cell Lymphoma

Обзор

1. Study Title: A Study on the Efficacy and Safety of Autocrine p40 CD19/CD20 Dual-Targeting Chimeric Antigen Receptor T-Cells (CD19/CD20-CAR.p40-T) in Relapsed/Refractory B-Cell Lymphoma 2. Study Objectives: * Primary Objective: To evaluate the safety of CD19/CD20 dual-targeting CAR.p40-T cell therapy in patients with relapsed/refractory B-cell lymphoma. * Secondary Objective: To evaluate the efficacy of CD19/CD20 dual-targeting CAR.p40-T cell therapy in patients with relapsed/refractory B-cell lymphoma. 3. Participant Intervention: * Participants will receive lymphodepleting chemotherapy (FC regimen: Fludarabine + Cyclophosphamide) on Days -5, -4, and -3 relative to the planned CD19/CD20-CAR.p40-T cell infusion or CD19 CAR.p40-T cell infusion. The CAR-T cell infusion will be administered 72 hours after the completion of the FC chemotherapy.

Подробное описание

A prospective, interventional Phase I/IIa clinical study to evaluate the safety and efficacy of autocrine p40 CAR-T cells targeting dual CD19/CD20 in refractory/relapsed B-cell lymphoma. A total of 20 patients aged 18 to 75 years with pathologically confirmed B-cell lymphoma (refractory/relapsed) will be enrolled. The total dose of CAR-T cells is 0.5-2×10\^6 CAR-T cells/kg, administered as a single intravenous infusion. Eligible subjects (n=20) will be assigned by the investigator to receive either CD19CD20 CAR.p40-T injection or CD19 CAR.p40-T injection.

* Primary Endpoint\*\*: To assess treatment-emergent adverse events (TEAEs) within 30 days after intravenous infusion of CAR-T cells. * Secondary Endpoints\*\*:

* Objective response rate (ORR=CR+PR) within 8 weeks; * Overall survival (OS) and progression-free survival (PFS) at 6 months; * In vivo expansion and persistence kinetics of CAR-T cells.

Вмешательства

• Комбинированный продукт CAR-T cell
  Participants will receive lymphodepleting chemotherapy (FC regimen: Fludarabine + Cyclophosphamide) on Days -5, -4, and -3 relative to the planned CD19/CD20-CAR.p40-T or CD19-CAR.p40-T cell infusion. The CAR-T cell infusion will be administered 72 hours after the completion of the FC chemotherapy.

Первичные конечные точки

• TEAEs [Срок оценки: From date of initial treatment to the 30 days after treatment]

Вторичные конечные точки (1)

• Disease-related clinical responses [Срок оценки: From date of enrollment until the date of clinical responses,up to 2 years]

Критерии участия

Критерии включения

• Aged between 15 and 75 years old, regardless of gender;
• Diagnosed with relapsed/refractory B-cell lymphoma according to the 2020 World Health Organization (WHO) diagnostic criteria;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2;
• Expected survival time of ≥ 3 months;
• Confirmation of CD20 expression in tumor cells by flow cytometry/immunohistochemistry;
• Patients tolerant to CD19 CAR-T cell therapy or those with low CD19 expression;
• No severe heart, lung, liver, or kidney diseases;
• Capable of understanding and willing to sign the informed consent form for this trial;
• No contraindications to peripheral blood apheresis for the subject;
• Having clearly measurable and evaluable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 standard;
• The subject must have received standard first- and second-line treatment regimens;
• Not having received antibody-based drug treatment within 2 weeks before cell therapy.

Критерии исключения

• History of allergy to any component in the cell product;
• The following conditions in the blood routine examination: White blood cell count (WBC) ≤ 1×10⁹/L, absolute neutrophil count (ANC) ≤ 0.5×10⁹/L, absolute lymphocyte count (ALC) ≤ 0.5×10⁹/L, platelet count (PLT) ≤ 25×10⁹/L;
• The following conditions in laboratory tests: including but not limited to, total serum bilirubin ≥ 1.5 mg/dl; serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2.5 times the upper limit of normal; serum creatinine ≥ 2.0 mg/dl;
• Patients with heart failure classified as grade III or IV according to the New York Heart Association (NYHA) classification criteria; or left ventricular ejection fraction (LVEF) < 50% as detected by echocardiography;
• Abnormal lung function with oxygen saturation < 92% under room air;
• Myocardial infarction, cardiac angioplasty or stenting, unstable angina pectoris, or other clinically severe heart diseases within 12 months before enrollment;
• Grade 3 hypertension with poorly controlled blood pressure despite drug treatment;
• History of craniocerebral trauma, disturbance of consciousness, epilepsy, severe cerebral ischemia or intracerebral hemorrhagic diseases;
• Patients with autoimmune diseases, immunodeficiency, or other conditions requiring immunosuppressive agent treatment;
• Presence of uncontrolled active infection;
• Previous use of any CAR-T cell product or other genetically modified T cell therapies;
• Vaccination with live vaccines within 4 weeks before enrollment;
• Subjects positive for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and Treponema pallidum particle agglutination assay (TPPA)/rapid plasma reagin (RPR), as well as HBV carriers;
• History of alcohol abuse, drug abuse, or mental illness in the subject;
• The subject participated in any other clinical study within 3 months before joining this clinical study;
• Female subjects with any of the following conditions: a) Currently pregnant or breastfeeding; or b) Having a pregnancy plan during the trial period; or c) Being fertile but unable to take effective contraceptive measures;
• Other circumstances that, in the opinion of the investigator, make the subject unsuitable for participation in this study.

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

Организация здравоохранения

Центры проведения

Китай · 1 центр

• Shenzhen University General Hospital — Шэньчжэнь

Идентификаторы

NCT: NCT07097207 · 111 · 111

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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