This study aims to assess the safety profile of in vivo BCMA/GPRC5D-targeted CAR-T cell immunotherapy in patients with relapsed or refractory plasma cell neoplasms.
This is a single-center, open-label, single-arm, prospective study designed to evaluate the safety of in vivo BCMA/GPRC5D-targeted CAR-T cell immunotherapy in patients with relapsed or refractory plasma cell neoplasms. The study employs a dose-escalation design to assess safety, tolerability, and preliminary efficacy. Safety assessments primarily focus on potential adverse events (AEs) following infusion of SL4903 injection, including the number of cases, incidence rates, and severity of cytokine release syndrome, immune effector cell therapy-related neurotoxicity, hematologic toxicity, organ toxicity, ect. Efficacy assessments will include overall objective response rate (ORR), event-free survival (EFS), overall survival (OS), progression-free survival (PFS), duration of complete remission, relapse rate, and mortality rate. Exploratory analyses will focus on characterizing the in vivo kinetics of CAR-T cells and the clonal evolution of plasma cell neoplasms during and after consolidation treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Administration of in vivo BCMA/GPRC5D tandem dual CAR-T cells. Three dose levels (dose A, dose B, dose C) will be evaluated using a standard 3+3 dose-escalation design.
Number and incidence rate with Each Grade of Cytokine Release Syndrome (CRS)
CRS severity will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading. The grade ranges from 1 to 4, where a higher grade indicates a worse outcome.
Time frame: 1 month after treatment
Dose-limiting toxicities (DLTs)
Dose limiting toxicity will be assessed after injection
Time frame: 1 month after treatment
Number and incidence rate of Each Grade of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)
ICANS severity is graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading, which incorporates the Immune Effector Cell-Associated Encephalopathy (ICE) assessment. The ICE score ranges from 0 to 10, with higher scores indicating better cognitive function. ICANS grade ranges from 1 to 4, where a higher grade indicates a worse outcome.
Time frame: 1 month after treatment
Number and incidence rate of Treatment-Associated Adverse Events (AEs)
All other AEs would be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).
Time frame: 1 years after treatment
Overall Objective Response Rate (ORR)
Overall objective response rate (ORR) refers the sum of the proportions of complete remission (CR) and partial remission (PR).
Time frame: Day 14, Day 28, Month 2 , Month 3, Month 6, Month 9, Month 12, Month 18, Month24 after the treatment
overall survival (OS)
Overall survival (OS) refers to the time from the start of treatment to the death of the patient for any reason.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: 2 years after treatment
progression free survival (PFS)
Progression free survival (PFS) refers to the time from treatment to the first disease progression or death of the patient for any reason.
Time frame: 2 years after treatment
duration of response (DOR)
Duration of Response (DOR) refers to the time from the first assessment of plasma cell neoplasms as a complete or partial response to the first assessment of PD (Progressive Disease) or death from any cause.
Time frame: 2 years after treatment
time to progression (TTP)
Time to progression (TTP) refers to the time from treatment to the first plasma cell neoplasms progression.
Time frame: 2 years after treatment
recurrence rate
The recurrence rate refers to the proportion of patients with plasma cell neoplasms recurrence after treatment.
Time frame: 2 years after treatment
Cmax of CAR-T Cells
CAR-T kinetics would be detected by flow cytometry or qPCR in peripheral blood or bone marrow at each important time points. Cmax is the peak expansion value of CAR-T cells. Cmax is the peak expansion value of CAR-T cells.
Time frame: 1 month after treatment
Tmax of CAR-T Cells
CAR-T kinetics would be detected by flow cytometry or qPCR in peripheral blood bone marrow at each important time points. Tmax is the time of the occurrence of expansion peak.
Time frame: 1 month after treatment
AUC(0-28d)
AUC(0-28d) is the area under the peripheral blood CAR-T cell concentration versus time curve calculated from the time of treatment to 28 days post-treatment, using the linear trapezoidal method.
Time frame: 1 month after treatment