Clinical Study of LV009 Injection in the Treatment of Recurrent/Refractory CD19 Positive Blood Tumors

Overview

This clinical trial is designed as a single-arm, open-label, single-center investigator-initiated early-phase clinical study, whose primary objective is to evaluate the safety of LV009 Injection in the treatment of subjects with relapsed/refractory CD19-positive hematolymphoid malignancies. Eligible subjects who have signed the informed consent form will receive an infusion of LV009 Injection. Blood samples will be collected from the subjects before and after the infusion for the evaluation of safety, pharmacokinetics, pharmacodynamics, immunogenicity and other indicators. In addition to the baseline period, during the treatment phase, efficacy assessments will be conducted at 4 weeks, 2 months, 3 months, 6 months after the infusion of the study drug, and then at a frequency of once every 3 months from the 6th to the 24th month. Tumor assessments will be continued until the occurrence of disease progression (PD), initiation of new anti-tumor therapy, death, intolerable toxicity, decision by the investigator or voluntary withdrawal of the subject, whichever comes first.

All adverse events will be recorded from the start of study drug infusion in subjects until 3 months after drug infusion, disease progression/relapse, initiation of new anti-disease therapy, or study conclusion, whichever comes first. During the period from 3 months after drug administration, disease progression/relapse, or initiation of new anti-disease therapy (whichever occurs first) to the end of the study, only adverse events related to the study product will be collected. Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) will be graded according to the Lee Criteria (2019), while all other adverse events (AEs) will be graded based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. Dose Escalation: A dose escalation study will be conducted according to the designed dose levels. With the exception of the first dose cohort, where only 1 subject will be enrolled from the perspective of benefit-risk assessment and ethics, all other dose cohorts will adopt the traditional "3+3" dose escalation model. Four fixed dose levels of LV009 Injection will be used for escalation, namely: 0.3×10⁹, 0.6×10⁹, 1.2×10⁹, and 2.4×10⁹ Transduction Units (TU). Dose Escalation Rules: Only 1 subject will be enrolled at the 0.3×10⁹ TU dose level. If a Dose-Limiting Toxicity (DLT) event occurs during the DLT observation period (28 days after cell infusion), the acceleration phase will be terminated and the "3+3" dose escalation study will be initiated. In the "3+3" dose escalation phase, if no DLTs are observed among 3 evaluable subjects, escalation to the next higher dose cohort is permitted. If 1 DLT occurs among 3 evaluable subjects, an additional 3 evaluable subjects need to be enrolled. If ≥1 further DLT occurs (i.e., the total number of subjects with DLT reaches ≥2), the previous dose level will be defined as the Maximum Tolerated Dose (MTD). A total of 10-19 subjects with CD19-positive hematolymphoid malignancies will be enrolled in the study. Within each dose cohort, the next subject may be administered the study drug only after the previous subject has completed a minimum of 14 days of safety observation. After the last subject in each dose cohort completes the DLT assessment within 28 days following a single administration, enrollment and treatment for the next dose cohort may commence only after the Safety Review Committee (SRC) reviews and approves the move based on the integration of clinical safety data. If 1 DLT occurs among 3 subjects in a dose cohort, 3 additional subjects need to be enrolled in the same dose cohort (resulting in a total of 6 subjects completing DLT assessment in that cohort): If no DLTs occur in the 3 additional subjects, dose escalation will continue; If 1 DLT occurs in the 3 additional subjects, dose escalation will be terminated; If \>1 DLT occurs in the 3 additional subjects, dose escalation will be terminated, and enrollment of 3 additional subjects at one dose level lower will be required for DLT assessment. If the investigators, through a comprehensive evaluation of the safety, tolerability, and pharmacokinetic data of subjects in a dose cohort, deem it necessary to expand the sample size of that cohort to further observe its safety and pharmacokinetic profile, the cohort may be expanded to a maximum of 6 subjects after reaching a consensus with the sponsor through consultation.