Dual CD19 and CD20 CAR-T therapy for relapsed or refractory aggressive B-cell lymphoma

An Open and Dose-escalation Early Clinical Study of CD19 and CD20 CAR-T Cell Therapy for Relapsed or Refractory Aggressive B-cell Lymphoma

This trial will try a CAR-T treatment that targets both CD19 and CD20 for adults whose aggressive B-cell lymphoma has relapsed or not responded to prior therapies.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Peking University People's Hospital (other)
• Drugs / interventions: rituximab, chemotherapy, prednisone, chimeric antigen receptor, CAR-T
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07344818 on ClinicalTrials.gov

What this trial studies

This open-label, early phase 1 trial tests autologous CAR-T cells engineered to recognize both CD19 and CD20 in adults with relapsed or refractory aggressive B-cell lymphoma. A 3+3 dose-escalation design is used to evaluate safety and preliminary anti-tumor activity and to determine a recommended phase 2 dose (RP2D). Eligible patients must have received prior anthracycline-containing chemotherapy and anti-CD20 therapy and have measurable disease with tumor expression of CD19 and/or CD20. Treatments, infusions, and early safety monitoring (including assessments for cytokine release syndrome and neurotoxicity) will be conducted at the enrolling hospital in Beijing.

Who should consider this trial

Good fit: Adults aged 18 or older with relapsed or refractory aggressive B-cell lymphoma who have received at least two prior lines of therapy (or prior autologous stem cell transplant), have measurable disease expressing CD19 and/or CD20, an ECOG 0-2, adequate organ function, and life expectancy of at least 12 weeks are the intended participants.

Not a fit: Patients whose tumors lack CD19 and CD20 expression, who are too frail or have uncontrolled infections or major organ dysfunction, or who cannot tolerate intensive monitoring may not benefit from this therapy.

Why it matters

Potential benefit: If successful, the dual-target CAR-T could increase response rates and lower the risk of relapse due to loss of a single antigen.

How similar studies have performed: Early-phase clinical and preclinical work on dual-target or multi-target CAR-T approaches has shown promise in reducing antigen-loss relapse, but larger controlled data are still limited.

Eligibility criteria

Inclusion Criteria:

1. The subject or his/her legal guardian is able to understand and voluntarily sign the informed consent form (ICF).
2. Male or female subjects aged ≥18 years at the time of signing the ICF.
3. An expected life expectancy of at least 12 weeks.
4. An ECOG performance status of 0-2 at the time of signing the ICF.
5. A diagnosis of relapsed or refractory aggressive B-cell lymphoma at the time of signing the ICF. Subjects must have previously received treatment with anthracycline-containing chemotherapy and rituximab (or other CD20-targeted agents), and must have experienced relapse or progression after at least two prior lines of therapy or autologous hematopoietic stem cell transplantation (ASCT).
6. Presence of measurable positive lesions as defined by the Lugano criteria.
7. Lymphoma lesions confirmed by biopsy to screening demonstrating expression of CD19 and/or CD20.
8. Adequate major organ function.
9. contraception.

Exclusion Criteria:

1. Lymphoma involving only the central nervous system (CNS) (except for secondary CNS lymphoma).
2. History of CNS disorders.
3. History of autoimmune disease requiring systemic immunosuppressive therapy within 4 weeks prior to signing the ICF.
4. Presence of any uncontrolled active infection at the time of signing the ICF or within 2 weeks prior to leukapheresis, requiring antibiotic, antiviral, or antifungal treatment.
5. Evidence of active infection, including: HBV DNA、Positive anti-HCV antibody with detectable HCV RNA、Positive HIV antibody、Positive cytomegalovirus (CMV) DNA、Positive Epstein-Barr virus (EBV) DNA、Positive both treponemal-specific and non-specific serologic tests for syphilis.
6. Clinically significant cardiovascular disease.
7. Known hypersensitivity to any component of the investigational products used in this study.
8. Receipt of any disease-related investigational therapy or other systemic antitumor therapy prior to leukapheresis and within 5 half-lives of the drug.
9. Requirement for systemic corticosteroids (at a dose equivalent to ≥20 mg/day of prednisone) or other immunosuppressive agents within 2 weeks prior to signing the ICF, within 2 weeks prior to leukapheresis, or during the study.
10. Major surgery (excluding routine biopsy) within 4 weeks prior to signing the ICF, or planned major surgery during the study period.
11. History of another primary malignancy within 5 years prior to signing the ICF, except for:

    1. Adequately treated and cured carcinoma in situ of the cervix;
    2. Localized basal cell carcinoma or squamous cell carcinoma of the skin.
12. Receipt of a live attenuated vaccine within 4 weeks prior to signing the ICF, or planned vaccination with a live attenuated vaccine during the screening period.
13. Any condition or complication that, in the investigator's opinion, may affect protocol compliance or make the subject unsuitable for participation in the study.
14. Pregnant or breastfeeding women.

Where this trial is running

Beijing, Beijing Municipality

• Peking University People's Hospital — Beijing, Beijing Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Xiaodong Mo, PhD

Conditions: R/R Aggressive B-cell Lymphoma, CD19+CD20 dual CAR-T, B-NHL, CAR-T