This is an investigator-initiated trial aimed at assessing the safety and efficacy of ultra-fast autologous CD19-targeted CAR-T cells in the treatment of refractory systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a serious autoimmune disease that can lead to extensive damage in multiple organs and systems, ultimately resulting in disability and even death. Currently, the primary treatment for SLE relies on glucocorticoids and immunosuppressants to alleviate symptoms. However, due to the absence of a curative treatment, patients typically need to remain on medication indefinitely. In recent years, biological agents such as belimumab and rituximab have been introduced for the treatment of SLE, but these treatments cannot completely eliminate autoimmune B cells in the bone marrow, leading to unsatisfactory overall outcomes. Furthermore, discontinuing these drugs can lead to disease relapse, and there is still no cure for SLE, leaving patients facing the challenges of lifelong medication and an incurable disease. CAR-T therapy is an adoptive cell therapy that uses genetic modification technology to reprogram T cells and eliminate target cells expressing disease-related antigens through antigen-specific recognition. Since 2019, CAR-T cell therapy has been successfully applied to autoimmune diseases. Clinical studies have demonstrated that CD19-targeted CAR-T cells hold significant therapeutic potential for SLE. Compared with traditional CAR-T cells, ultra-fast CAR-T, relying on an innovative CAR-T manufacturing system, can produce CAR-T cells in an extremely short period of time (with a preparation time of only 10 minutes). The purpose of this study is to assess the safety and efficacy of the ultra-fast autologous CD19-targeted CAR-T cells in the treatment of refractory SLE.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Three dose groups (1.5×10\^5/kg, 5×10\^5/kg, 10×10\^5/kg) were set up, starting from the low dose group climbing to explore the safe and effective dose.
Affiliated Drum Tower Hospital, Medical School of Nanjing University
Nanjing, Jiangsu, China
RECRUITINGThe safety of CAR-T cell therapy in patients with refractory SLE [Safety]
Types, frequency and severity of adverse events.
Time frame: 3 months
The changes from baseline in SLEDAI-2K [efficacy]
Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI-2K) is from 0 to 105 points. The higher score means the stronger disease activity.
Time frame: 6 months
The changes from baseline in PGA [efficacy]
Physician Global Assessment(PGA) is a continuous visual analogue scale with 0, 1, 2, and 3 scales. "0" indicates no disease activity and "3" indicates the most severe disease activity.
Time frame: 6 months
The changes from baseline in BILAG-2004 [efficacy]
British Isles Lupus Assessment Group Index 2004(BILAG-2004) consists of 8 systems, each of which is classified as A, B, C and D respectively. "A" indicates that the condition is highly active and requires active treatment. "B" indicates that the condition is active and requires close monitoring or symptomatic treatment. "C" indicates a stable condition. "D" indicates that the system is not involved.
Time frame: 6 months
The number of patients with SRI-4 response [efficacy]
The definition of SRI-4 response: SLEDAI-2K ≥ 4-Point improvement; PGA with no worsening (\<0.3 point increase); BILAG 2004 with no new A domain score and no more than 1 new B domain scores.
Time frame: 3 months
The number of patients with LLDAS [efficacy]
The definition of LLDAS: SLEDAI-2K ≤ 4 and no disease activity in major organs (kidneys, central nervous system, heart and lungs), and no vasculitis or fever; no new disease activity symptoms were added compared with previous disease assessments; PGA ≤ 1; irrespective of serology; with permitted use of low-dose glucocorticoids (prednisolone ≤ 7.5 mg/day), and/or stable immunosuppressives and biologics.
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Time frame: 6 months
The number of patients with DORIS [efficacy]
The definition of DORIS: SLEDAI-2K = 0 ; PGA \< 0.5 ; irrespective of serology; with permitted use of antimalarials, low-dose glucocorticoids (prednisolone ≤ 5 mg/day), and/or stable immunosuppressives and biologics.
Time frame: 6 months
The changes of anti-ds-DNA antibody after infusion [efficacy]
Time frame: 6 months
The changes of 24h urine protein after infusion [efficacy]
Time frame: 6 months
The changes of serum complement C3 and C4 after infusion [efficacy]
Time frame: 6 months
Cmax of CAR-T cells [PK parameter]
The peak plasma concentration (Cmax) of amplified CAR-T cells in peripheral blood after infusion.
Time frame: 3 months
Tmax of CAR-T cells [PK parameter]
The time of amplified CAR-T cells in peripheral blood to reach the maximum concentration (Tmax).
Time frame: 3 months
AUC28d/90d of CAR-T cells [PK parameter]
The area under the plasma concentration-time curve from 28 to 90 days after infusion (AUC28d/90d).
Time frame: 3 months
The degree of B cell depletion [PD parameter]
The degree of B cell depletion at various time points.
Time frame: 3 months
The concentration levels of IL-6 [PD parameter]
CAR-T-related serum cytokines such as IL-6.
Time frame: 3 months
The concentration levels of CRP [PD parameter]
Time frame: 3 months
The concentration levels of ferritin [PD parameter]
Time frame: 3 months