This is a single arm, open-label, dose escalation and expansion study to evaluate the safety, tolerability and preliminary efficacy of autologous chimeric antigen receptor T (CAR-T) cells targeting CD19/CD22/BCMA(BZE2204) in patients with relapsed or refractory active autoimmune diseases, including idiopathic inflammatory myopathies(IIM), immune thrombocytopenia(ITP), systemic lupus erythematosus(SLE).
This is a single arm, open-label, dose escalation and expansion exploratory study, the primary objective is to evaluate the safety and tolerability of BZE2204 in patients with active relapsed or refractory autoimmune diseases, and determine the maximum tolerated dose (MTD) or recommended dose(RD) for future study. For the secondary objectives, pharmacokinetics(PK), pharmacodynamics (PD) and preliminary will be evaluated. This study flow comprises of a screening phase( ≤28 days prior to apheresis), apheresis phase (occur upon enrollment, ≤10 days prior to infusion), baseline phase(2-3days before the infusion), BZE2204 CAR-T cells infusion on Day0,safety and efficacy assessments phase (Day1 to Month6), long-term follow-up phase (Month6\~Month12).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of BZE2204 CAR T cells. On day0 subjects will receive a single dose BZE2204 CAR T cells by intravenous (IV) injection.
Shanghai Mengchao Cancer Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGThe frequency and severity of adverse events(AE) and serious adverse events(SAE)
Time frame: From leukapheresis to 6 months post CAR-T infusion
The frequency of dose-limiting toxicity(DLT)
Time frame: Day0 to Day28
Chimeric antigen receptor T cell (CAR-T) levels in peripheral blood at each time point.
Time frame: Day0-Month6 post infusion
Chimeric antigen receptor transgene levels in peripheral blood at each time point
Time frame: Day0-Month6 post infusion
Cytokines levels of IL-2(interleukin), IL-4, IL-6,IL-8, IL-10, IL-12p70, IL-13, IL-1β, TNF-a, IFN-r in peripheral blood at each time point.
Time frame: Day-3 to Month6 post infusion
B cell levels in peripheral blood at each time point
Time frame: Day-3 to Month6 post infusion
Immunoglobulins in peripheral blood at each time point
Time frame: Day-3 to Month6 post infusion
The level of muscle enzymes AST(aspartate transaminase), ALT(alanine transaminase), LDH(lactate dehydrogenase), CK(creatine kinase) in peripheral blood at each time point in idiopathic inflammatory myopathies (IIM)
Time frame: Day-3 to Month6 post infusion
The time of stopping steroids, immunosuppressants for autoimmune disease post infusion
Time frame: Day0-Month6 post infusion
The proportion of subjects with idiopathic inflammatory myopathies(IIM) achieving 2016 total improvement score(TIS) mild, moderate, major improvement; the time to the improvement and the duration of improvement.
Time frame: Month3, Month6
The proportion of subjects with immune thrombocytopenia(ITP) achieving complete remission
Time frame: Month3, Month6
The proportion of subjects with immune thrombocytopenia(ITP) achieving partial remission
Time frame: Month3, Month6
The proportion of subjects with systemic lupus erythematosus(SLE) achieving SLE Responder Index-4(SRI-4); the time to response and the duration of the response
Time frame: Month3, Month6
The change of SLE Disease Activity Index 2000(SLEDAI-2K) post infusion
Time frame: Month3, Month6
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