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

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

1. Study Title:

   A Study on the Efficacy and safety of CD19/CD20 CAR/TRuC-T in Relapsed/Refractory B-Cell Lymphoma

2. Study Objectives:

   Primary Objective: To evaluate the safety of CD19/CD20 CAR/TRuC-T cell therapy in patients with relapsed/refractory B-cell lymphoma.

   Secondary Objective: To evaluate the efficacy of CD19/CD20 CAR/TRuC-T cell therapy in patients with relapsed/refractory B-cell lymphoma.

   Exploratory Objective: To assess in vivo expansion and persistence of infused CD19/CD20 CAR/TRuC-T cells.

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/TRuC-T cell infusion. The CAR/TRuC-T cell infusion will be administered 72 hours after the completion of the FC chemotherapy.

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:

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

Subjects meeting any of the following criteria will be excluded:

1. History of allergy to any component of the cell product;

2. 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;

3. 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;

4. New York Heart Association (NYHA) Class III or IV heart failure, or left ventricular ejection fraction (LVEF) <50% on echocardiography;

5. Abnormal pulmonary function, with oxygen saturation <92% on room air;

6. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant severe cardiac disease within 12 months prior to enrollment;

7. Grade 3 hypertension with poor blood pressure control despite medication;

8. History of craniocerebral trauma, disturbance of consciousness, epilepsy, severe cerebral ischemia, or cerebral hemorrhagic disease;

9. Presence of autoimmune disease, immunodeficiency, or other conditions requiring immunosuppressive therapy;

10. Presence of uncontrolled active infection;

11. Prior treatment with any CAR-T cell product or other genetically modified T-cell therapy;

12. Receipt of a live vaccine within 4 weeks prior to enrollment;

13. Positive for HIV, HBV, HCV, or TPPA/RPR, or HBV carrier status;

14. History of alcohol abuse, drug abuse, or psychiatric illness;

15. Participation in any other clinical study within 3 months prior to enrollment in this study;

16. Female subjects meeting any of the following conditions:

    1. currently pregnant or breastfeeding;
    2. planning to become pregnant during the study period; or
    3. of childbearing potential and unwilling or unable to use effective contraception;

17. Any other condition that, in the investigator's judgment, makes the subject unsuitable for participation in this study.