Study of Ultra-Fast CD19 CAR-T Therapy for Refractory SLE

Study of Ultra-Fast Autologous CD19-targeted Chimeric Antigen Receptor T (CAR- T) Therapy for Refractory Systemic Lupus Erythematosus

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.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Biological: CD19 CAR-T cells

Detailed Description

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 diseaserelated 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
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jianhua Mao, MD; Phone Number: 13516819071; Email: maojh88@zju.edu.cn
• Study Contact Backup: Name: Xue He; Phone Number: 15088688407; Email: hexue1119@163.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310052
      • Recruiting
      • Children's Hospital of Zhejiang University School of Medicine
      • Contact: Xue He; Phone Number: 15088688407; Email: hexue1119@163.com
      • Contact: Jianhua Mao; Phone Number: Prof 0571-56555983; Email: maojh88@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age: ≥ 5 years old, and no gender limitation;
• Diagnosed with SLE according to the 2019 EULAR/ACR SLE classification criteria, and still in moderate to severe disease activity despite ≥3M of high dose glucocorticoids(prednisone≥1mg/kg/d or other equivalent amount of other steriod), hydroxychloroquine and at least 2 DMARDs(include cyclophosphamide, mycophenolate mofetil, azathioprine, methotrexate, cyclosporin, tacrolimus, sirolimus, leflunomide, telitacicept, Beliumab, and rituximab) or intolerant to standard treatments;
• SLEDAI-2K score≥8 points;

• The functions of important organs are basically normal:

  1. Cardiac function: Left ventricular ejection fraction (LVEF) ≥55% with no obvious abnormality in electrocardiogram;
  2. Renal function: eGFR≥30mL/min/1.73m2;
  3. Liver function: AST and ALT≤3.0 ULN, total Bilirubin (TBIL) in serum ≤2.0×ULN;
  4. Lung function: no serious lung lesions, SpO2≥92%;
• Meet the standards of leukapheresis or intravenous blood collection, and no contraindication for leukapheresis;
• Negative pregnancy test for female subjects of childbearing age, and agree to take effective contraceptive measures the first year after CAR-T infusion;
• Participants or their guardians agrees to participate in the clinical trial and sign the informed consent form which indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study.

Exclusion Criteria:

• Central nervous system (CNS) disease: CNS neurolupus requires intervention within 60 days);
• Severe acute nephritis: patients who have accepted or was undergoing renal replacement therapy within 3 months prior to transfusion; or in the investgator's opinion, patients who is likely to have significant kidney disease within 3 moths of the study which need high dose glucocorticoid (prednisone dose≥1mg/kg/day or equivalent amount of other steriod), cyclophosphamide, or mycophenolate mofetil treatment;
• Have a history of congenital heart disease 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;
• Uncontrollable infection, or active infection that requires systemic treatment within 3 months prior to screening;
• Received organ transplantation or hematopoietic stem cell transplantation within 3 months prior to screening, or ≥Grade 2 GVHD within 2 weeks prior to screening;
• Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal reference value range; or hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range; or positive for human immunodeficiency virus (HIV) antibodies; or syphilis test positive;
• Suffered from macrophage activation syndrome(MAS) within 1 month prior to screening (except for those whose safety risks have been ruled out by the researcher after treatment);
• Received CAR-T treatment (except for those whose safety risks have been ruled out by the researchers after treatment);
• Suffered from active pulmonary tuberculosis at screening;
• Received live vaccine within 4 weeks prior to screening;
• Positive in Blood pregnancy test;
• Previous or concurrent malignancy;
• Patients who participated in other clinical study within 3 months prior to screening;
• Any other conditions that the investigators deem it unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAR-T treatment group; This trial was designed as an open, single-arm, single-center, dose-increasing trial.	Biological: CD19 CAR-T cells; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The safety of CAR-T cell therapy in patients with refractory SLE [Safety]	Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs and other clinical manifestation assessed by CommonTerminology Criteria for Adverse Events (CTCAE) v5.0.	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.	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.	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.	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.	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.	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.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of remission of lupus nephritis [efficacy]	The degree of remission of lupus nephritis includes complete response(CR), primary efficacy renal response(PERR) and partial response(PR).	6 months
The changes of anti-ds-DNA antibody after infusion [efficacy]		6 months
The changes of 24h urine protein after infusion [efficacy]		6 months
The changes of C3 and C4 after infusion [efficacy]		6 months
Cmax of CAR-T cells [PK parameter]	The peak plasma concentration (Cmax) of amplified CAR-T cells in peripheral blood after infusion.	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).	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).	3 months
The degree of B cell depletion [PD parameter]	The degree of B cell depletion at various time points.	3 months
The concentration levels of IL-6 [PD parameter]	CAR-T-related serum cytokines include IL-6.	3 months
The concentration levels of CRP [PD parameter]		3 months
The concentration levels of ferritin [PD parameter]		3 months

Collaborators and Investigators

• Sponsor: The Children's Hospital of Zhejiang University School of Medicine
• Investigators: Principal Investigator: Jianhua Mao, MD, Children's Hospital of Zhejiang University School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: September 28, 2025
• First Submitted That Met QC Criteria: November 16, 2025
• First Posted (Actual): November 18, 2025

Study Record Updates

• Last Update Posted (Actual): November 18, 2025
• Last Update Submitted That Met QC Criteria: November 16, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: CAR-T; CD19
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: PBC097

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No