Overview

The aim of this study was to analyze the safety and efficacy of CD3-CD20 bispecific antibody-based therapy in combination with CD19-CAR-T cells for the treatment of relapsed and refractory B-cell Non-Hodgkin's （B-NHL） lymphoma.

The main questions it aims to answer：

1. The safety of CD3-CD20 bispecific antibody-based therapy in combination with CD19-CAR-T cells in B-NHL;
2. The effect of different doses of bispecific antibody maintenance therapy on CAR-T cell expansion.

Eligibility

Inclusion Criteria:

• The patient has fully understood the study and voluntarily signed the informed consent form (ICF)
• Must meet the diagnostic criteria for relapsed and refractory B-NHL and have evaluable disease lesions, in addition to the following characteristics for different types of B-NHL:

A, Diffuse large B-cell Lymphoma:

        Patients with histologically confirmed DLBCL; Patients who must have received
        ,anthracyclines CD20 monoclonal antibodies and BTK inhibitors and other Drug therapy, and
        have received at least two lines of treatment and relapsed, not relieved or progressed
        within 24 months after the last line of treatment;
        B, Relapsed and Refractory Follicular lymphoma (FL):
        Tissue Biopsy proved FL: grade 1-3a; Must have received anthracyclines and CD20 monoclonal
        antibody Drug therapy, and have received at least two lines of treatment and relapsed, not
        remitted or progressed within 24 months after the last line of treatment;
        C, Relapsed and Refractory Marginal zone lymphoma (MZL):
        Histologically unequivocally confirmed MZL; Must have received anthracyclines and CD20
        monoclonal antibody Drug therapy, and have received at least two lines of treatment and
        relapsed, not remitted or progressed within 24 months after the last line of treatment;
        D, Relapsed and refractory Mantle cell lymphoma (MCL):
        Histologically confirmed MCL; Relapsed or refractory after at least 2 lines of therapy
        (including anti-CD20 monoclonal antibody, anthracyclines or bendamustine, and BTKi);
        E, Relapsed and refractory CLL:
        Histologically confirmed CLL; Patients who have received at least Immunochemotherapy and
        have Drug therapy to both BTK inhibitors and BCL2 inhibitors Drug resistance;
        F, Relapsed and refractory WM:
        Patients with histologically confirmed WM; Patients who must have received anthracyclines,
        CD20 monoclonal antibodies and BTK inhibitors and other Drug therapy, and have received at
        least two lines of treatment and relapsed, not relieved or progressed within 24 months
        after the last line of treatment;
          -  ECOG score 0-1
          -  Laboratory test: Neutrophils 0.5 x 10 ^ 9/L; platelets 30 x 10 ^ 9/L; Bilirubin total
             2 x upper limit; GPT/Glutamic-oxaloacetic transferase 3 x upper limit. Creatinine
             clearance ≥ 30 mL/min.
          -  The expected survival time of patients is ≥ 6 months;
        Exclusion Criteria:
          -  Neoplasm malignant other than B-NHL (except active central nervous system lymphoma)
             diagnosed or treated within the past year; Patients who received anti Neoplasm therapy
             (including chemotherapy, targeted therapy, hormone therapy, traditional Chinese
             medicine with anti neoplasm activity, etc.) or participated in other clinical trials
             and received the investigational drug within 4 weeks before the first use of the
             investigational drug;
          -  Liver renal impairment not related to lymphoma: GPT (ALT) > 3 times the upper limit of
             normal, glutamic-oxaloacetic transferase (AST) > 3 times the upper limit of normal,
             bilirubin total (TBIL) > 2 times the upper limit of normal, serum creatinine clearance
             rate < 30ml/min;
          -  Other serious medical diseases that will affect the study (such as uncontrolled
             Diabetes mellitus, gastric ulcer, other serious heart lung disease, etc.), and the
             right to decide belongs to the investigator.
          -  Cardiac function and disease meet one of the following conditions:
        A, Long QTc syndrome or QTc interval > 480 MS; B, Complete left bundle branch block, grade
        II or III AV block; C, Serious, uncontrolled arrhythmia requiring drug therapy; D, New York
        Heart Association Heart disorder grade ≥ III; E, Cardiac Ejection Fraction (LVEF) less than
        50%; F, Ischaemia, unstable Angina pectoris, history of severe unstable Ventricular
        arrhythmia or any other Arrhythmia requiring treatment, history of clinically significant
        Pericardial disease, or Electrocardiogram evidence of acute Myocardial infarction or active
        conduction system abnormalities within 6 months prior to recruitment;
          -  Known history of Infection human Immunodeficiency virus (HIV) or active Hepatitis B
             virus (HBV) Infection, or any uncontrolled active Injection requiring intravenous
             Systemic infection of antibiotics; Patients in the past 14 days received a large
             surgery (excluding lymph node Biopsy) or expected treatment in the need for a large
             Surgery;
          -  Previous or current other neoplasm malignant (except effectively controlled skin Basal
             cell carcinoma without melanoma, breast/In situ cancer of cervix, and other
             effectively controlled Neoplasm malignant without treatment within the past five years
          -  Pregnancy or lactating women, women of childbearing age who did not take contraception
             measures;
          -  Hypersensitivity to the drugs or ingredients used;