An Open and Dose-escalation Early Clinical Study of CD19 and CD20 CAR-T Cell 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

To observe the efficacy and safety of dual-target chimeric antigen receptor T cells in the treatment of refractory or relapsed aggressive B-cell lymphoma

In this study, anti-CD19 and anti-CD20 dual target CAR-T cell therapy will be explored for patients with relapsed/refractory aggressive B-cell lymphoma. In this study, the 3+3 dose climbing mode will be used to explore the safety and efficacy of dual-target CAR-T cells in r/r B-NHL therapy at different doses. The RP2D dose will be determined after the relevant data is summarized。

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.