This study is aimed to explored the safety and efficacy of 7×19-THEMIS CAR-T cell therapy for large B-cell lymphoma and to conduct an exploratory comparison of the 3-month objective response rate (ORR) and complete remission rate (CR rate) between the experimental cohort and the historical control cohort (NCT04833504).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
70
IL7 and CCL19 Armed anti-CD19 CAR-T with coexpressing Themis
The Second Affiliated Hospital,School of Medicine,Zhejiang University, Hangzhou, Zhejiang 310009
Hangzhou, Zhejiang, China
RECRUITINGDetermination of the Recommended Phase II Dose (RP2D)
Based on the incidence of DLTs, CAR-T cell kinetics, preliminary efficacy, and safety data from the Phase Ib dose-escalation phase, the Safety Review Committee (SRC) determined the RP2D following a comprehensive evaluation.
Time frame: Up to 3 months
Objective Response Rate (ORR)
At 3 months (±7 days) after infusion, the proportion of patients achieving complete remission (CR) or partial remission (PR) was assessed according to the Lugano 2014 criteria, and a descriptive comparison was made with the historical control cohort.
Time frame: Up to 3 months
Complete Remission Rate (CR Rate)
At 3 months (±7 days) after infusion, the proportion of patients who achieved complete remission (CR) was assessed according to the Lugano 2014 criteria, and a descriptive comparison was made with the historical control cohort.
Time frame: Up to 3 months
Incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) graded according to ASTCT 2019 criteria
The incidence and severity of CRS and ICANS will be assessed according to the American Society for Transplantation and Cellular Therapy (ASTCT) 2019 consensus grading criteria. The incidence of each grade (Grades 1-4) will be summarized, with particular attention to the incidence of Grade ≥3 CRS and Grade ≥3 ICANS.
Time frame: up to 28 days
Incidence and duration of Grade ≥3 hematologic toxicities assessed according to CTCAE version 5.0
The incidence and duration of Grade ≥3 neutropenia, anemia, and thrombocytopenia will be assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: up to 28 days
Incidence of clinically significant infections requiring anti-infective treatment or hospitalization
The incidence of bacterial, fungal, and viral infections requiring anti-infective treatment or hospitalization will be recorded and summarized.
Time frame: up to 28 days
Progression-Free Survival (PFS)
Progression-free survival is defined as the time from CAR-T cell infusion to the first documented disease progression (PD) or death from any cause, whichever occurs first. Median PFS and PFS rates at 12 and 24 months will be estimated using the Kaplan-Meier method.
Time frame: up to 2-5 years
Overall Survival (OS)
Overall survival is defined as the time from CAR-T cell infusion to death from any cause. Median OS and OS rates at 12 and 24 months will be estimated using the Kaplan-Meier method.
Time frame: up to 2-5 years
Duration of Response (DOR)
Among participants who achieve complete response (CR) or partial response (PR), duration of response is defined as the time from the first documented response to disease progression or death from any cause, whichever occurs first. Median DOR will be estimated using the Kaplan-Meier method.
Time frame: up to 2-5 years
In Vivo Kinetics of CAR-T Cells
Measurement of CAR-T Cell Counts in Peripheral Blood and Comparison of Kinetic Parameters
Time frame: up to 2-5 years
Serum Cytokine Dynamics
Measure the concentrations of cytokines such as IL-6, IFN-γ, IL-7, and CCL19 in serum at various time points following infusion.
Time frame: day-5,day4,day7,day11,day14,day18,day21,day28,month 3
B-Cell Recovery
Determine the absolute count of CD19+CD20+ cells in peripheral blood to assess the dynamics of B-cell recovery following infusion.
Time frame: month1, month3, month6, month9, months12, month24, year3 and year5
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.