Evaluation of GI001 for Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

Study Design and Methodology This is an investigator-initiated, open-label, single-arm, dose-escalation, and expansion exploratory clinical study. The study utilizes an "Accelerated Titration" combined with a standard "3+3" design to evaluate the safety, tolerability, and preliminary anti-tumor activity of GI001 injection-an innovative in vivo CAR-T therapy-in patients with relapsed or refractory (r/r) CD19+ B-cell malignancies. Dose Escalation Phase Four dose levels have been pre-specified: 1E8, 3E8, 7E8 or 1E9 TU 1. Accelerated Titration: The first subject will be enrolled at the starting dose ( TU). If no Dose-Limiting Toxicity (DLT) or Grade 2 treatment-related adverse events occur within the 28-day DLT observation period, the study may proceed to the next dose level with a single subject. 2. Standard 3+3 Design: If a DLT or significant toxicity (as defined in the protocol) is observed during the accelerated phase, the study will transition to a traditional 3+3 escalation model to ensure subject safety and more robustly determine the Maximum Tolerated Dose (MTD). Dose Expansion Phase Upon completion of the escalation phase and determination of the MTD or Recommended Dose for Expansion (RDE), an additional 12-18 subjects will be enrolled to further characterize the safety profile and provide a more comprehensive assessment of preliminary efficacy. Treatment and Monitoring Subjects will receive a single intravenous infusion of GI001. Due to the risk of Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), subjects must be hospitalized for intensive monitoring for at least 14 days post-infusion. Clinical assessments, including physical examinations, vital signs, and laboratory tests (hematology, biochemistry, and coagulation), will be conducted at frequent intervals. Pharmacokinetics (PK) and Pharmacodynamics (PD) A central laboratory will analyze peripheral blood, saliva, and urine samples to: * Quantify the expansion and persistence of GI001 CAR-T cells using qPCR and/or Flow Cytometry. * Monitor systemic cytokine levels (e.g., IL-6, IFN-, TNF-) to correlate with safety and efficacy outcomes. * Assess immunogenicity (Anti-Drug Antibodies) and potential viral shedding (RCL testing) to ensure long-term biological safety. Long-Term Follow-up Following the initial 24-month efficacy and safety evaluation period, subjects will be invited to participate in a long-term safety follow-up study for up to 15 years, in accordance with regulatory guidelines for gene therapy products, to monitor for delayed adverse events such as secondary malignancies or prolonged B-cell aplasia.