Exploratory Clinical Study on the Safety and Efficacy of CD19X CAR-T Cell Injection in the Treatment of Relapsed/Refractory Large B-Cell Lymphoma

Обзор

This study is an open-label, single-arm, prospective, exploratory clinical trial involving patients with relapsed/refractory large B-cell lymphoma, aiming to preliminarily assess the safety and efficacy of CAR-T cell infusion.

Подробное описание

This study is an open-label, single-arm, prospective, exploratory clinical trial targeting patients with relapsed/refractory large B-cell lymphoma. It plans to enroll 3 participants, where the investigator will administer a dose of 1-2×10\^6 CAR cells/kg of CAR-T cell infusion and follow up to observe related data on post-treatment adverse reactions and therapeutic effects, with the aim of preliminarily evaluating the safety and efficacy of the CAR-T cell infusion.

Вмешательства

• Препарат CD19X CAR-T
  Eligible participants receive lymphodepletion pretreatment 3 to 5 days before the therapy. The recommended pretreatment regimen is fludarabine (25-30 mg/m²) and cyclophosphamide (250-300 mg/m²). Antihistamines are administered before infusion. The plan is to enroll 3 patients with relapsed/refractory large B-cell lymphoma, who will be evaluated by the investigator and treated with 1-2 × 10\^6 CAR cells/kg of CAR-T cell infusion.

Первичные конечные точки

• Incidence and severity of adverse events [Срок оценки: Within 28 days after CAR-T infusion]

Вторичные конечные точки (6)

• Efficacy indicators [Срок оценки: At 1 and 3 months after CAR-T infusion]
• Efficacy indicators [Срок оценки: At 1 and 3 months after CAR-T infusion]
• Cell Metabolic Kinetics Indicators [Срок оценки: On the 7th, 10th, 14th, and 28th days after treatment]
• Cellular Metabolic Kinetics Indicators [Срок оценки: On the 7th, 10th, 14th, and 28th days after treatment]
• Cellular Metabolic Kinetics Indicators [Срок оценки: Day 28 after treatment]
• Exploratory indicators [Срок оценки: The CAR-T single-cell phenotype and clonal characteristics are tested on the day of cell infusion. Follow-up is conducted on D10 and D28 after infusion, once a month from M2 to M3, every three months from M6 to Y1, and every three months from Y1 to Y2.]

Критерии участия

Критерии включения

• 1\. The participant has given consent and signed the informed consent form, and is willing and able to comply with planned visits, research treatments, laboratory tests, and other trial procedures;
• 2\. Clinically diagnosed with relapsed/refractory large B-cell lymphoma, and confirmed by pathology or flow cytometry that tumor cells express CD19, including: diffuse large B-cell lymphoma (DLBCL), transformed indolent B-cell lymphoma to DLBCL (excluding Richter transformation), and meeting the following criteria (satisfying one of the first two and the third): i. Relapse ≥6 months after achieving remission following first-line adequate therapy or ≥12 months after stem cell transplantation; ii. Patients who did not achieve remission after at least 2-4 cycles of first-line chemotherapy combined with high-risk factors (double-expressor lymphoma, double-hit lymphoma, TP53 gene mutation or deletion, IPI score ≥3), or disease progression during first-line therapy, or progression within 6 months after achieving remission from prior sufficient therapy, or relapse within 12 months after achieving remission from stem cell transplantation; iii. The participant has received the following treatments for LBCL after diagnosis:

• Anti-CD20 monoclonal antibody;
• Combination chemotherapy containing anthracyclines.
• 3\. Age 18 years and above, both male and female;
• 4\. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
• 5\. Expected survival of more than 3 months from the date of signing the informed consent form;
• 6\. HGB ≥ 60 g/L (blood transfusion allowed); LYM ≥ 0.3\*10\^9/L;
• 7\. Liver and kidney function, as well as cardiopulmonary function, must meet the following requirements:

• Creatinine ≤ 1.5×ULN;
• Left ventricular ejection fraction ≥ 50%;
• Blood oxygen saturation > 90%;
• Total bilirubin ≤ 1.5×ULN; ALT and AST ≤ 2.5×ULN;
• 8\. Study participants planning pregnancy must agree to use contraception before enrollment in the study and for one year after CAR-T cell infusion; participants should notify the investigator immediately if they become pregnant or suspect they are pregnant.

Критерии исключения

• 1\. Severe heart failure with left ventricular ejection fraction <50%;
• 2\. History of severe pulmonary dysfunction;
• 3\. Concurrent progressive malignant tumors;
• 4\. Severe infections that cannot be effectively controlled;
• 5\. Severe autoimmune diseases or congenital immunodeficiency;
• 6\. History of CAR-T cell immunotherapy;
• 7\. Active hepatitis (hepatitis B virus DNA \[HBV-DNA\] or hepatitis C virus RNA \[HCV-RNA\] levels above the detection limit);
• 8\. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), or syphilis infection;
• 9\. History of severe allergic reactions to biological products (including antibiotics);
• 10\. Allogeneic hematopoietic stem cell transplant patients who still have acute graft-versus-host disease (GvHD) one month after discontinuing immunosuppressive drugs.
• 11\. Women who are pregnant or breastfeeding, or planning to become pregnant within 12 months;
• 12\. Individuals with other serious physical or mental illnesses or abnormal laboratory test results that may increase the risk of participating in the study, interfere with the study results, or whom the researcher considers 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

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07447726 · IIT2025136

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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