CD19/CD20 Dual-Target in Vivo CAR-T Lentiviral Product in the Treatment of Relapsed/Refractory B-cell Malignancies

This is an open-label, dose expansion study to assess the safety, tolerability, and efficacy of CD19/CD20 Dual-Target in vivo CAR-T Lentiviral product in adult patient with relapsed or refractory B cell Malignancies. Subjects who meet the eligibility criteria will receive a single dose of CD19/CD20 Dual-Target in vivo CAR-T Lentiviral product. The study will include the following sequential phases: screening, bridging therapy (if needed), treatment, and follow-up.

Inclusion criteria

• Subjects voluntarily participate in clinical studies; Fully informed of this study and signed informed consent; Informed consent form must be obtained prior to initiation of any study-related tests or procedures that are not part of the standard treatment for the subject's disease; Good compliance and cooperation with follow-up.
• Age greater than or equal to 18.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• At least one measurable tumor lesion.
• Eligible subjects shall meet the criteria and qualification requirements of any one of the expansion cohorts as follows:

• Cohort 1: Relapsed or refractory large B-cell lymphoma patients who have received at least one line of systemic therapy and have not undergone CAR-T therapy;
• Cohort 2: High-risk large B-cell lymphoma patients in the first-line setting (who have completed 2 cycles of standard first-line systemic immunochemotherapy);
• Cohort 3: Relapsed or refractory mantle cell lymphoma patients treated with at least two lines of systemic therapy;
• Cohort 4: Exploratory cohort including relapsed or refractory indolent lymphoma and other B-cell malignancies.
• Life expectancy≥ 3 months
• Clinical laboratory values meet screening visit criteria
• Adequate organ function;

Exclusion criteria

Subject eligible for this study must not meet any of the following criteria:

• Prior antitumor therapy with insufficient washout period ;
• Prior treatment with lentiviral vector-based gene therapies;
• Patients who are positive for hepatitis B surface antigen (HBsAg), hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C antibody (HCV-Ab), hepatitis C virus ribonucleic acid (HCV RNA), and human immunodeficiency virus antibody (HIV-Ab).
• Known life-threatening allergic reaction, hypersensitivity reaction, or intolerance to study drug excipients and related excipients, including but not limited to DMSO; or those with a history of severe allergic reactions in the past (such as hypersensitivity reactions, or those with severe immune-related reactions such as the need for glucocorticoids to prevent anaphylaxis as assessed by the investigator).
• Lactating women;