Autocrine p40 CD19/CD20 dual-targeting CAR-T therapy for relapsed or refractory B-cell lymphoma

Study on the Efficacy and Safety of Autocrine p40 Chimeric Antigen Receptor T Cells Targeting CD19 and CD20 (CD19CD20-CAR.p40-T) in Refractory B-Cell Lymphoma

This will test a dual-targeting CD19/CD20 autocrine p40 CAR-T cell treatment in adults whose B-cell lymphoma has returned or not responded to prior therapies.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shenzhen University General Hospital (Academic / other)
• Drugs / interventions: CAR-T, Chimeric Antigen Receptor, chemotherapy, Cyclophosphamide, Fludarabine
• Locations: 1 site (Shenzhen, Other (Non U.s.))
• Trial ID: NCT07097207 on ClinicalTrials.gov

What this trial studies

This Phase I/IIa interventional trial will enroll about 20 adults with relapsed or refractory B-cell lymphoma to receive a single intravenous infusion of autocrine p40 CAR-T cells targeting CD19/CD20 (total dose 0.5–2×10^6 CAR-T cells/kg) after lymphodepleting chemotherapy (fludarabine + cyclophosphamide). Eligible patients are assigned by the investigator to receive either the dual-targeting CD19/CD20 CAR.p40-T or a CD19-only CAR.p40-T product, with safety (treatment-emergent adverse events within 30 days) as the primary endpoint. Secondary endpoints include objective response rate within 8 weeks, six-month overall and progression-free survival, and in vivo CAR-T expansion and persistence. The trial includes standard pre-infusion apheresis and hospital-based monitoring for cytokine release syndrome and other CAR-T–related toxicities.

Who should consider this trial

Good fit: Ideal candidates are adults with pathologically confirmed relapsed or refractory B-cell lymphoma who express CD20, have ECOG performance status 0–2, have received standard first- and second-line treatments, and can tolerate apheresis and lymphodepleting chemotherapy.

Not a fit: Patients with absent CD20 expression, severe heart/lung/liver/kidney disease, very limited life expectancy, or who cannot tolerate apheresis or lymphodepletion are unlikely to benefit from this therapy.

Why it matters

Potential benefit: If successful, this approach could produce deeper or more durable remissions by targeting two B-cell antigens and reducing relapse due to antigen escape.

How similar studies have performed: CD19-targeted CAR-T therapies have produced meaningful responses in B-cell lymphoma, and some dual-targeting approaches show promise, but autocrine p40 CD19/CD20 designs are relatively novel with limited prior data.

Eligibility criteria

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.

Where this trial is running

Shenzhen, Other (Non U.s.)

• Shenzhen University General Hospital — Shenzhen, Other (Non U.s.), China (Recruiting)

Study contacts

• Principal investigator: Lixin Wang, PHD — Shenzhen University General Hospital
• Study coordinator: lixin wang

Conditions Relapsed/Refractory B-cell Lymphoma