Relapsed/Refractory B-cell Lymphoma
Conditions
Brief summary
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
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.
Interventions
COMBINATION_PRODUCTCAR/TRuC-T
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.
Sponsors
Shenzhen University General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TEAEs | From date of initial treatment to the 30 days after treatment | Adverse events during treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease-related clinical responses | From date of enrollment until the date of clinical responses,up to 2 years | Disease-related clinical responses include CR/PR/SD/PD |
Countries
China
Contacts
CONTACTLIXIN LI, PHD
Outcome results
None listed