Efficacy and Safety of CD19/CD20 CAR/TRuC-T in Relapsed/Refractory B-Cell Lymphoma

Detailed Description:

This is a prospective, interventional Phase I/II clinical study designed to evaluate the safety and efficacy of CD19/CD20 CAR/TRuC-T cell therapy in patients with relapsed/refractory B-cell lymphoma. A total of 20 patients aged 18-75 years with relapsed/refractory B-cell lymphoma will be enrolled. All patients must have histopathologically confirmed disease and positive CD20 expression in tumor tissue.

CD19/CD20 CAR/TRuC-T cells will be administered as a single intravenous infusion at a total dose of 0.5-2 × 10^6 CAR-T cells/kg. Eligible subjects (N=20) will be assigned by the investigator to receive CD19/CD20 CAR/TRuC-T cell infusion.

Endpoints:

• Primary Endpoint:

o Incidence and severity of treatment-emergent adverse events (TEAEs) within 30 days after CD19/CD20 CAR/TRuC-T cell infusion.

• Secondary Endpoints:

• Objective response rate (ORR = CR + PR) assessed within 8 weeks after infusion;
• Overall survival (OS) and progression-free survival (PFS) at 6 months;
• In vivo expansion and persistence kinetics of infused CD19/CD20 CAR/TRuC-T cells.

Inclusion criteria

Subjects must meet all of the following criteria to be enrolled:

• Aged 18 to 75 years, regardless of sex;
• Histologically confirmed relapsed/refractory B-cell lymphoma according to the 2020 World Health Organization (WHO) classification;
• ECOG performance status of 0-2;
• Expected survival of at least 3 months;
• CD20 expression on tumor cells confirmed by flow cytometry and/or immunohistochemistry;
• Patients who are resistant/refractory to CD19 CAR-T cell therapy or have low CD19 expression;
• No severe cardiac, pulmonary, hepatic, or renal disease;
• Able to understand and willing to sign the informed consent form for this study;
• No contraindications to peripheral blood mononuclear cell collection/apheresis;
• At least one measurable and evaluable lesion according to RECIST 1.1;
• Must have previously received standard first-line and second-line therapy;
• No antibody-based therapy within 2 weeks prior to cell therapy. Exclusion Criteria

Subjects meeting any of the following criteria will be excluded:

• History of allergy to any component of the cell product;
• Abnormal complete blood count meeting any of the following: WBC ≤1 × 10⁹/L, ANC ≤0.5 × 10⁹/L, ALC ≤0.5 × 10⁹/L, or PLT ≤25 × 10⁹/L;
• Laboratory abnormalities including, but not limited to, any of the following: total serum bilirubin ≥1.5 mg/dL; ALT or AST >2.5 times the upper limit of normal; serum creatinine ≥2.0 mg/dL;
• New York Heart Association (NYHA) Class III or IV heart failure, or left ventricular ejection fraction (LVEF) <50% on echocardiography;
• Abnormal pulmonary function, with oxygen saturation <92% on room air;
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant severe cardiac disease within 12 months prior to enrollment;
• Grade 3 hypertension with poor blood pressure control despite medication;
• History of craniocerebral trauma, disturbance of consciousness, epilepsy, severe cerebral ischemia, or cerebral hemorrhagic disease;
• Presence of autoimmune disease, immunodeficiency, or other conditions requiring immunosuppressive therapy;
• Presence of uncontrolled active infection;
• Prior treatment with any CAR-T cell product or other genetically modified T-cell therapy;
• Receipt of a live vaccine within 4 weeks prior to enrollment;
• Positive for HIV, HBV, HCV, or TPPA/RPR, or HBV carrier status;
• History of alcohol abuse, drug abuse, or psychiatric illness;
• Participation in any other clinical study within 3 months prior to enrollment in this study;
• Female subjects meeting any of the following conditions:

• currently pregnant or breastfeeding;
• planning to become pregnant during the study period; or
• of childbearing potential and unwilling or unable to use effective contraception;
• Any other condition that, in the investigator's judgment, makes the subject unsuitable for participation in this study.