Study of Therapeutic Efficacy of Anti-CD19 CAR-T Cells in Refractory Systemic Lupus Erythematosus

A Clinical Study on the Safety and Efficacy of Chimeric Antigen Receptor T Cell Injection Targeting CD19 Gene in the Treatment of Refractory Systemic Lupus Erythematosus

This is an investigator-initiated trial aimed at assessing the safety of anti-CD19 CAR-T cells in the treatment of refractory systemic lupus erythematosus.

Study Overview

• Status: Active, not recruiting
• Conditions: Systemic Lupus Erythematosus; CAR-T Cell Therapy
• Intervention / Treatment: Biological: anti-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. Children with SLE are particularly at risk of organ damage, especially to the kidneys, and tend to have a more severe and protracted course of the disease compared to adults.

Currently, the primary treatment for SLE relies on glucocorticoids and immunosuppressants to alleviate symptoms. However, due to the absence of a curative treatment, patients often require lifelong medication. In recent years, biological agents such as belimumab and rituximab have been introduced for the treatment of SLE, but these agents cannot completely eliminate autoimmune B cells in the bone marrow, leading to unsatisfactory overall outcomes. Furthermore, stopping the drugs can lead to relapse, and there is still no cure for SLE, leaving patients facing the challenges of lifelong medication and an incurable disease.

Since 2019, CAR-T cell therapy has been successfully applied to autoimmune diseases. Clinical studies have demonstrated that targeted CD19 CAR-T cells hold significant therapeutic potential for SLE. These cells effectively slow down the pathological progression of SLE and can also effectively treat severe cases. Furthermore, targeted CD19 CAR-T cells are also expected to restore the immune system in SLE patients, potentially allowing them to discontinue lifelong medication and avoid serious long-term side effects of drugs like hormones and immunosuppressants. The purpose of this study is to assess the safety and efficacy of the anti-CD19 CAR-T cells in the treatment of refractory SLE.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310052
      • Children's Hospital, Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

1. Age: ≥5 years old.

2. Refractory SLE Diagnosis:

   1. Diagnosed with SLE according to the 2019 EULAR/ACR classification criteria.
   2. Exhibit persistent moderate to severe disease activity (defined as a SLEDAI-2K score ≥ 8).
   3. Demonstrated failure or to achieve target disease control (LLDAS or remission) after a minimum of 6 months of standard-of-care therapy, including: high doses of glucocorticoids (≥1mg/kg/day prednisone or equivalent), hydroxychloroquine, and at least two DMARDs (including cyclophosphamide, MMF, azathioprine, methotrexate, cyclosporine, tacrolimus, sirolimus, leflunomide, tocilizumab, belimumab, and rituximab) for at least 6 months; or intolerant to conventional treatments.

   Note: Patients may also be eligible if they are documented as intolerant to these conventional treatments.

3. Disease Severity Validation: To ensure a "refractory" status, patients must satisfy at least one of the following:

   1. Active Major Organ Involvement (e.g., biopsy-proven Lupus Nephritis Class III, IV, or V; CNS lupus; or refractory hematological cytopenias).
   2. Steroid Dependence: Inability to taper glucocorticoid dose below 0.5 mg/kg/day (or equivalent) without a disease flare.

4. Organ Function:

   1. Cardiac: LVEF ≥ 55 %, with no significant clinical abnormalities on ECG.
   2. Renal: Estimated glomerular filtration rate (eGFR) 30 mL/min/1.73m2.
   3. Liver: AST and ALT ≤ 3.0 ULN, and total bilirubin ≤ 2.0 ULN.
   4. Pulmonary: No severe lung disease, with oxygen saturation (SpO2) ≥ 92% on room air.
5. Apheresis Suitability: Must meet institutional criteria for leukapheresis and have no contraindications to peripheral blood mononuclear cell (PBMC) collection.
6. Contraception: Females of childbearing age must have a negative urine pregnancy test at screening and agree to use effective contraceptive measures from enrollment until 1 year after MC-1-50 cell infusion.
7. Informed Consent: Voluntary written informed consent must be obtained from the subject (if applicable) and their lawful guardians prior to any screening procedures.

Exclusion Criteria:

1. Prior Cell Therapy: Previous treatment with any CAR-T cell therapy or other genetically modified effector cell products.

2. Neurological/CNS Involvement:

   1. Active central nervous system (CNS) lupus requiring clinical intervention within 60 days of screening (including seizures, delirium, or cerebrovascular events).
   2. Evidence of significant structural CNS damage on MRI or a history of severe seizures that may lower the threshold for ICANS.

3. Severe Renal Impairment and Fibrosis:

   1. Receiving renal replacement therapy (dialysis) within 3 months prior to infusion.
   2. Irreversible Renal Damage: Documented high chronicity on baseline biopsy (e.g., Chronicity Index >6/12) or extensive renal fibrosis, as these patients are unlikely to achieve functional recovery despite immunological remission.
   3. Significant nephropathy likely requiring high-dose glucocorticoids (≥1mg/kg/day prednisone or equivalent) or intensified DMARDs within 3 months of infusion.

4. Cardiac Conditions:

   Serious congenital heart disease; acute myocardial infarction within 6 months of screening; severe arrhythmias (e.g., multifocal premature ventricular tachycardia); large pericardial effusion; severe myocarditis; or hypotension requiring pressor agents at screening.

5. Pulmonary Pathology:

   1. History of severe lung disease, including significant bronchiectasis, emphysema, or advanced interstitial lung disease (ILD) at baseline.
   2. Resting oxygen saturation (SpO2 <92%).
6. Concomitant Therapy: Requirement for long-term glucocorticoids or immunosuppressive therapy for conditions other than SLE.
7. Infections: Active infections requiring systemic treatment or uncontrollable infections (bacterial, fungal, or viral) within 1 week before screening.
8. Transplantation/GVHD: Solid organ or hematopoietic stem cell transplantation within 3 months before screening; or presence of Grade 2 or higher acute graft-versus-host disease (GVHD) within 2 weeks of screening.

9. Viral and Serological Markers:

   1. Positive HBsAg or HBcAb with detectable HBV-DNA.
   2. Positive HCV antibody with detectable HCV-RNA.
   3. Positive HIV antibody, syphilis test, or detectable CMV-DNA.

10. Other Clinical Conditions:

    1. Macrophage activation syndrome (MAS) within 1 month before screening.
    2. Vaccination with a live vaccine within 4 weeks before screening.
    3. Malignancies or other severe systemic diseases.
11. Pregnancy: Positive blood pregnancy test at screening.
12. Trial Participation: Enrollment in another clinical trial within 3 months prior to this study.
13. Investigator Discretion: Any other condition that, in the opinion of the investigator, makes the subject unsuitable for the study or puts them at undue risk.

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 is an open-label, single-arm, multicenter, investigator-initiated study. The study will primarily evaluate the Target Dose of 1×10^5 CAR+ cells/kg. The majority of subjects will be enrolled at this level to characterize efficacy and safety. Two exploratory dose levels-Low Dose (0.3×10^5 CAR+ cells/kg) and High Dose (3×10^5 CAR+ cells/kg)-are reserved for dose modification based on safety signals or preliminary efficacy data.

Biological: anti-CD19-CAR-T cells; The study will primarily evaluate the Target Dose of 1×10^5 CAR+ cells/kg. The majority of subjects will be enrolled at this level to characterize efficacy and safety. Two exploratory dose levels-Low Dose (0.3×10^5CAR+ cells/kg) and High Dose (3×10^5 CAR+ cells/kg)-are reserved for dose modification based on safety signals or preliminary efficacy data.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The safety of CAR-T cells in refractory Systemic Lupus Erythematosus	Incidence, type, and severity of adverse events. The grading of CRS and neurotoxicity follow the ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells, published by ASTCT in 2019. Other AEs are graded using the NCI CTCAE 5.0.	3 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The efficacy of CAR-T cells in refractory Systemic Lupus Erythematosus	Proportion of participants achieving an SRI-4 response at 3 months post-infusion, defined by: a ≥4-point reduction in SLEDAI-2K score; no worsening in Physician's Global Assessment (increase <0.3); and no new major organ involvement as assessed by BILAG.	3 months
LLDAS response rate.	LLDAS response rate, defined as the percentage of subjects who meet the following conditions simultaneously after infusion: ①SLEDAI-2K score ≤4, with no activity in major organ systems (including kidney, central nervous system, heart and lungs), no vasculitis and no fever; ② no new lupus disease activity compared with the previous assessment; ③PGA score ≤1; ④serological activity permitted; ⑤ prednisolone dose ≤7.5mg daily and well-tolerated standard maintenance doses of immunosuppressive drugs or biological agents permitted.	12 months
DORIS response rate.	DORIS response rate, defined as the percentage of subjects who meet the following conditions simultaneously after infusion: ① clinical SLEDAI-2K score =0; ② PGA score <0.5; ③ serological activity permitted; ④low-dose glucocorticoid (i.e. prednisolone ≤5mg daily) and well-tolerated standard maintenance doses of antimalarials, immunosuppressive drugs or biological agents permitted.	12 months
Evaluate the Pharmacokinetics parameters.	PK parameters: The highest concentration (Cmax) of CD19-targeted CAR-T cells expanded in peripheral blood after infusion, the time to reach the highest concentration (Tmax).	3 months
Evaluate the Pharmacodynamics parameters.	PD parameters: The degree of B cell depletion at various time points, the concentration levels of CAR-T-related serum cytokines.	3 months
Changes in serological biomarkers related with SLE	Changes in serological biomarkers, including anti-dsDNA antibodies and complement C3/C4 levels, which used for evaluating the SLEDAI score	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune reconstitution following MC-1-50 infusion	To explore the impact of MC-1-50 on immune system reconstruction, including the characterization of reconstituted B-cell subsets (Naive vs. Memory) and T-cell phenotypes.	6 months
Duration of response	Duration of response, defined as time from first documented response to disease progression.	12 months
Optional repeat renal biopsy ≥3 months post-infusion.	Optional repeat renal biopsy ≥3 months post-infusion, with assessment of activity and chronicity indices, subject to separate informed consent.	12 months
Longitudinal changes in SLEDAI-2K scores over time.	Scores on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) range from 0 to 105, with higher scores indicating greater disease activity.	12 months

Collaborators and Investigators

• Sponsor: The Children's Hospital of Zhejiang University School of Medicine
• Collaborators: Chongqing Precision Biotech Co., Ltd
• Investigators: Principal Investigator: Jianhua Mao, MD, Children's Hospital, Zhejiang University School of Medicine

Publications and helpful links

General Publications

• Anders HJ, Saxena R, Zhao MH, Parodis I, Salmon JE, Mohan C. Lupus nephritis. Nat Rev Dis Primers. 2020 Jan 23;6(1):7. doi: 10.1038/s41572-019-0141-9.
• Kansal R, Richardson N, Neeli I, Khawaja S, Chamberlain D, Ghani M, Ghani QU, Balazs L, Beranova-Giorgianni S, Giorgianni F, Kochenderfer JN, Marion T, Albritton LM, Radic M. Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus. Sci Transl Med. 2019 Mar 6;11(482):eaav1648. doi: 10.1126/scitranslmed.aav1648.
• Jin X, Xu Q, Pu C, Zhu K, Lu C, Jiang Y, Xiao L, Han Y, Lu L. Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus. Cell Mol Immunol. 2021 Aug;18(8):1896-1903. doi: 10.1038/s41423-020-0472-1. Epub 2020 May 29.
• Mougiakakos D, Kronke G, Volkl S, Kretschmann S, Aigner M, Kharboutli S, Boltz S, Manger B, Mackensen A, Schett G. CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus. N Engl J Med. 2021 Aug 5;385(6):567-569. doi: 10.1056/NEJMc2107725. No abstract available.
• Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638. doi: 10.1016/j.bbmt.2018.12.758. Epub 2018 Dec 25.
• Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, Komanduri KV, Lin Y, Jain N, Daver N, Westin J, Gulbis AM, Loghin ME, de Groot JF, Adkins S, Davis SE, Rezvani K, Hwu P, Shpall EJ. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018 Jan;15(1):47-62. doi: 10.1038/nrclinonc.2017.148. Epub 2017 Sep 19.
• Mackensen A, Muller F, Mougiakakos D, Boltz S, Wilhelm A, Aigner M, Volkl S, Simon D, Kleyer A, Munoz L, Kretschmann S, Kharboutli S, Gary R, Reimann H, Rosler W, Uderhardt S, Bang H, Herrmann M, Ekici AB, Buettner C, Habenicht KM, Winkler TH, Kronke G, Schett G. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med. 2022 Oct;28(10):2124-2132. doi: 10.1038/s41591-022-02017-5. Epub 2022 Sep 15.

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2024
• Primary Completion (Actual): April 4, 2025
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: January 4, 2024
• First Submitted That Met QC Criteria: January 15, 2024
• First Posted (Actual): January 25, 2024

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: January 30, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

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

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
• product manufactured in and exported from the U.S.: No