This is an exploratory, open-label, single-arm Phase 1 clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of QT-219C. QT-219C is a universal allogeneic chimeric antigen receptor T-cell (CAR-T) product targeting both CD19 and BCMA. The study targets subjects with refractory B-cell-related autoimmune diseases, including systemic lupus erythematosus (SLE), multi-drug resistant nephrotic syndrome (NS), IgA nephropathy (IgAN), systemic sclerosis (SSc), and ANCA-associated vasculitis (AAV) .The research is divided into two phases: a dose-escalation phase and a dose-expansion phase. Dose Escalation: Utilizes a standard "3+3" design to evaluate potential recommended dose(RD) and identify dose-limiting toxicities (DLTs) .Treatment Procedure: Eligible subjects will receive a lymphodepleting conditioning regimen followed by a single intravenous infusion of QT-219C .Primary Objectives: The primary goals are to evaluate the safety profile, including the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and to assess clinical response rates at 90 days post-infusion .Follow-up: Subjects will be monitored for pharmacokinetics (cell expansion), pharmacodynamics (B-cell depletion), and long-term safety for up to two years .
1)Bone Marrow Function: a. Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L; b. Hemoglobin ≥ 60 g/L; c. Platelet count ≥ 30 × 10⁹/L.
2)Hepatic Function: ALT ≤ 3 × ULN (except when elevation is attributable to inflammatory myopathy); AST ≤ 3 × ULN (except when elevation is attributable to inflammatory myopathy); Total bilirubin ≤ 2.0 × ULN (≤ 3.0 × ULN allowed for Gilbert syndrome).
3)Renal Function: eGFR ≥ 30 mL/min/1.73 m².(Participants with eGFR < 30 mL/min/1.73 m² and/or those receiving renal replacement therapy may be considered eligible if, in the investigator's judgment, the potential benefit outweighs the risk and the participant or guardian provides fully informed consent.)
4)Cardiac Function: Echocardiography shows no significant structural abnormalities and left ventricular ejection fraction (LVEF) ≥ 55%.
1. Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, tocilizumab), or subjects with a history of severe allergic reactions.
2.Subjects with grade III or IV heart failure (NYHA classification).
3.Have a history of congenital heart disease or acute myocardial infarction within 6 months prior to screening; Or severe arrhythmias (including multisource frequent supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with moderate to massive pericardial effusion, serious myocarditis, etc; Or patients with unstable vital signs who need hypertensive drugs.
4. Uncontrollable infection, or active infection that requires systemic treatment at screening.
Single group
UCAR T-cell
Biological/VaccineA universal allogeneic CAR-T cell product targeting both CD19 and BCMA
Incidence of Dose-Limiting Toxicities (DLTs)
The number, frequency, and severity of DLTs experienced by subjects after the first infusion of QT-219C. DLTs are defined by NCI-CTCAE 5.0 and ASTCT consensus for CRS and neurotoxicity.
Incidence of Adverse Events (AEs)
Evaluation of the number, frequency, and severity of all adverse events, including Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events (TRAEs), and Serious Adverse Events (SAEs).
Preliminary Clinical Efficacy at Day 90
Assessment of disease-specific clinical response rates : * SLE: Proportion of subjects achieving SRI-4, LLDAS, or DORIS criteria. * Nephrotic Syndrome/IgA Nephropathy: Proportion of subjects achieving Complete Remission (CR) or Partial Remission (PR)/Proteinuria Remission. * Systemic Sclerosis: Changes in CRISS scores. * ANCA-associated Vasculitis: Proportion of subjects achieving CR or PR.
Cmax of CAR-T cells [PK parameter]
The peak plasma concentration (Cmax) of amplified UCAR-T cells in peripheral blood after infusion.
Tmax of CAR-T cells [PK parameter]
The time of amplified UCAR-T cells in peripheral blood to reach the maximum concentration (Tmax).
AUC 0-28d of UCAR-T cells [PK parameter]
The area under the plasma concentration-time curve from 0 to 28 days after infusion (AUC0-28d).
The degree of B cell depletion [PD parameter]
The degree of B cell depletion at various time points.
Growth and Development Assessment
For subjects under 18 years of age, monitoring of changes in height.
Growth and Development Assessment
For subjects under 18 years of age, monitoring of changes in weight.
Growth and Development Assessment
For subjects under 18 years of age, monitoring of changes in Tanner stage.
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