study evaluates a biomarker-guided strategy to assign adults with refractory SLE to autologous CAR-T therapy targeting either CD19 or BCMA. Participants undergo centralized screening immunophenotyping to determine whether their disease appears B-cell-dominant (CD19-preferred) or plasma-cell-dominant (BCMA-preferred), followed by leukapheresis, lymphodepletion, and a single CAR-T infusion. The main goals are to assess safety, determine a recommended Phase 2 dose within each arm, and estimate remission rates by Week 24.
SLE is frequently sustained by autoreactive CD19-positive B cells, plasmablasts, and long-lived plasma cells. CD19-directed CAR-T can produce profound B-cell depletion and immune reset, whereas BCMA-directed CAR-T may better address plasma-cell-dominant disease, especially persistent autoantibody production or lupus nephritis after prior B-cell-depleting therapy. This example trial prospectively assigns participants to the target most likely to match their dominant pathogenic compartment. At screening, a central review committee evaluates flow cytometry target expression, serum autoantibody burden, complement levels, immunoglobulins, prior response to rituximab or similar agents, and renal/plasma-cell biomarkers where relevant. Each arm includes a safety lead-in with dose escalation followed by an expansion cohort at the recommended Phase 2 dose. All participants undergo leukapheresis, optional protocol-limited bridging therapy, fludarabine/cyclophosphamide lymphodepletion, single CAR-T infusion, inpatient monitoring, and follow-up through 52 weeks, plus separate long-term gene-modified-cell safety surveillance.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Autologous anti-CD19 CAR-T cells are patient-derived T lymphocytes that are genetically engineered to target CD19-expressing B cells. In clinical trials, a single intravenous infusion is administered at a protocol-defined dose (e.g., 1 × 10⁶ or 3 × 10⁶ CAR-positive viable T cells per kg) to evaluate safety, tolerability, and preliminary efficacy.
30 mg/m2/day IV on Days -5 to -3.
300 mg/m2/day IV on Days -5 to -3.
Peking University Shenzhen Hospital
Shenzhen, Guangdong, China
RECRUITINGDose-limiting toxicities (DLTs)
Incidence of protocol-defined DLTs, including product-related Grade 3 or higher non-hematologic toxicity and prolonged severe cytopenia.
Time frame: 28 days
Incidence and severity of cytokine release syndrome (CRS)
Incidence and severity of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, graded by ASTCT criteria.
Time frame: 28
Protocol-defined lupus response
Proportion of participants achieving DORIS remission without rescue therapy or, for those with active baseline LN, complete renal response without rescue therapy.
Time frame: 24 weeks
Complete renal response in LN subgroup
Renal response rate in participants with active lupus nephritis at baseline.
Time frame: 52 weeks
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