Relapsed/Refractory B-cell Lymphoma
Conditions
Brief summary
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.
Detailed description
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.
Interventions
COMBINATION_PRODUCTCAR-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.
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
1. Aged between 15 and 75 years old, regardless of gender; 2. Diagnosed with relapsed/refractory B-cell lymphoma according to the 2020 World Health Organization (WHO) diagnostic criteria; 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2; 4. Expected survival time of ≥ 3 months; 5. Confirmation of CD20 expression in tumor cells by flow cytometry/immunohistochemistry; 6. Patients tolerant to CD19 CAR-T cell therapy or those with low CD19 expression; 7. No severe heart, lung, liver, or kidney diseases; 8. Capable of understanding and willing to sign the informed consent form for this trial; 9. No contraindications to peripheral blood apheresis for the subject; 10. Having clearly measurable and evaluable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 standard; 11. The subject must have received standard first- and second-line treatment regimens; 12. Not having received antibody-based drug treatment within 2 weeks before cell therapy.
Exclusion criteria
1. History of allergy to any component in the cell product; 2. 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; 3. 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; 4. 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; 5. Abnormal lung function with oxygen saturation \< 92% under room air; 6. Myocardial infarction, cardiac angioplasty or stenting, unstable angina pectoris, or other clinically severe heart diseases within 12 months before enrollment; 7. Grade 3 hypertension with poorly controlled blood pressure despite drug treatment; 8. History of craniocerebral trauma, disturbance of consciousness, epilepsy, severe cerebral ischemia or intracerebral hemorrhagic diseases; 9. Patients with autoimmune diseases, immunodeficiency, or other conditions requiring immunosuppressive agent treatment; 10. Presence of uncontrolled active infection; 11. Previous use of any CAR-T cell product or other genetically modified T cell therapies; 12. Vaccination with live vaccines within 4 weeks before enrollment; 13. 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; 14. History of alcohol abuse, drug abuse, or mental illness in the subject; 15. The subject participated in any other clinical study within 3 months before joining this clinical study; 16. 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; 17. Other circumstances that, in the opinion of the investigator, make 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
Primary Contactlixin wang
Outcome results
None listed