This is an investigator-initiated, open-label, single-arm, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics (PD), and preliminary efficacy of an in vivo circular RNA chimeric antigen receptor T cell in adult participants with R/R B-cell malignancies.
This is an investigator-initiated, open-label, single-arm, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics (PD), and preliminary efficacy of an in vivo circular RNA chimeric antigen receptor T cell in adult participants with R/R B-cell malignancies. Investigational product (IP)will be explored across four dose levels (as described in the table below) in adult participants with R/R B-cell malignancies, including diffuse large B-cell lymphoma \[DLBCL\], follicular lymphoma \[FL\], mantle cell lymphoma \[MCL\], chronic lymphocytic leukemia \[CLL\]/small lymphocytic lymphoma \[SLL\], Waldenström macroglobulinemia \[WM\], and marginal zone lymphoma (MZL). The study consists of three periods: screening period, treatment period, and post-treatment follow-up period.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
In Vivo Circular RNA Chimeric Antigen Receptor (CAR) T Cell Therapy
The Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, China
RECRUITINGRuijin Hospital
Shanghai, China
NOT_YET_RECRUITINGIncidence and severity of treatment-emergent adverse events (TEAEs)
Count the number and percentage of participants with treatment-emergent adverse events (TEAEs). The severity of all TEAEs is graded according to CTCAE Version 5.0.
Time frame: From first dose of investigational product (IP) up to the end of study (Week 24 / EOS)
Incidence of dose-limiting toxicities (DLTs)
Count the number and percentage of participants who experience at least one dose-limiting toxicity (DLT) as defined by the study protocol.
Time frame: 28 days after the first dose of IP
Overall Response Rate (ORR)
Calculate the proportion of participants achieving Complete Response (CR) or Partial Response (PR). Tumor response is assessed per Lugano 2014 criteria, iWCLL 2018 criteria, and the 11th International WM Workshop criteria.
Time frame: From Week 4 through Week 24 (EOS)
Time to Response (TTR)
Evaluate the time interval from the first IP infusion to the first documented CR or PR.
Time frame: Up to Week 24 (EOS)
Duration of Response (DOR)
Evaluate the time interval from the first documented CR or PR to the first documented progressive disease (PD) or all-cause death, whichever occurs first.
Time frame: Up to Week 48 survival follow-up
Event-Free Survival (EFS)
Evaluate the time interval from the first IP infusion to the first documented PD, relapse, initiation of new anti-lymphoma therapy, or all-cause death, whichever occurs first.
Time frame: Up to Week 48 survival follow-up
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Progression-Free Survival (PFS)
Evaluate the time interval from the first IP infusion to the first documented PD or all-cause death, whichever occurs first.
Time frame: Up to Week 48 survival follow-up
Absolute count and percentage of CAR-expressing positive immune cells
Detect and analyze the absolute count and percentage of CAR-expressing positive immune cells in peripheral blood at each time point, and assess dynamic changes from baseline.
Time frame: From pre-dose baseline through Week 24 (EOS)
CD7 expression kinetics on immune cells
Dynamically detect CD7 expression levels on peripheral blood immune cells at each time point and analyze kinetic changes from baseline.
Time frame: From pre-dose baseline through Week 24 (EOS)
Overall Survival (OS)
Evaluate the time interval from the first IP infusion to all-cause death.
Time frame: Up to Week 48 survival follow-up
PK parameters of IP components
Determine the PK parameters of the circRNA component and cationic lipid component of the IP respectively.
Time frame: From pre-dose baseline through Week 24 (EOS)
Incidence of immunogenicity to IP
Count the number and percentage of participants with pre-existing antibodies (anti-PEG, anti-CAR, anti-CD7 VHH) and treatment-induced antibodies (anti-PEG, anti-CAR, anti-CD7 VHH) against IP.
Time frame: From pre-dose baseline through Week 24 (EOS)
Correlation between cytokine levels and treatment response adverse events(TRAE)
Detect serum cytokine levels and conduct exploratory correlation analysis between cytokine concentrations and clinical outcomes.
Time frame: From pre-dose baseline through Week 24 (EOS)