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

NCT06222853 | Active Not Recruiting Phase 1

• 1 other identifier: STEAM
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Systemic Lupus Erythematosus; CAR-T Cell Therapy

Keywords

Systemic Lupus Erythematosus; CAR-T

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• The efficacy of CAR-T cells in refractory Systemic Lupus Erythematosus

  3 months

• LLDAS response rate.

  12 months

• DORIS response rate.

  12 months

• Evaluate the Pharmacokinetics parameters.

  3 months

• Evaluate the Pharmacodynamics parameters.

  3 months

Other Outcomes (4)

• Immune reconstitution following MC-1-50 infusion

  6 months

• Duration of response

  12 months

• Optional repeat renal biopsy ≥3 months post-infusion.

  12 months

Study Arms (1)

CAR-T treatment group

EXPERIMENTAL

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

Interventions

anti-CD19-CAR-T cells BIOLOGICAL

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.

CAR-T treatment group

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: ≥5 years old.
• Refractory SLE Diagnosis:
• Diagnosed with SLE according to the 2019 EULAR/ACR classification criteria.
• Exhibit persistent moderate to severe disease activity (defined as a SLEDAI-2K score ≥ 8).
• 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.
• Disease Severity Validation: To ensure a "refractory" status, patients must satisfy at least one of the following:
• Active Major Organ Involvement (e.g., biopsy-proven Lupus Nephritis Class III, IV, or V; CNS lupus; or refractory hematological cytopenias).
• Steroid Dependence: Inability to taper glucocorticoid dose below 0.5 mg/kg/day (or equivalent) without a disease flare.
• Organ Function:
• Cardiac: LVEF ≥ 55 %, with no significant clinical abnormalities on ECG.
• Renal: Estimated glomerular filtration rate (eGFR) 30 mL/min/1.73m2.
• Liver: AST and ALT ≤ 3.0 ULN, and total bilirubin ≤ 2.0 ULN.
• Pulmonary: No severe lung disease, with oxygen saturation (SpO2) ≥ 92% on room air.
• Apheresis Suitability: Must meet institutional criteria for leukapheresis and have no contraindications to peripheral blood mononuclear cell (PBMC) collection.

You may not qualify if:

• Prior Cell Therapy: Previous treatment with any CAR-T cell therapy or other genetically modified effector cell products.
• Neurological/CNS Involvement:
• Active central nervous system (CNS) lupus requiring clinical intervention within 60 days of screening (including seizures, delirium, or cerebrovascular events).
• Evidence of significant structural CNS damage on MRI or a history of severe seizures that may lower the threshold for ICANS.
• Severe Renal Impairment and Fibrosis:
• Receiving renal replacement therapy (dialysis) within 3 months prior to infusion.
• 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.
• Significant nephropathy likely requiring high-dose glucocorticoids (≥1mg/kg/day prednisone or equivalent) or intensified DMARDs within 3 months of infusion.
• 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.
• Pulmonary Pathology:
• History of severe lung disease, including significant bronchiectasis, emphysema, or advanced interstitial lung disease (ILD) at baseline.
• Resting oxygen saturation (SpO2 \<92%).
• Concomitant Therapy: Requirement for long-term glucocorticoids or immunosuppressive therapy for conditions other than SLE.
• Infections: Active infections requiring systemic treatment or uncontrollable infections (bacterial, fungal, or viral) within 1 week before screening.

Sponsors & Collaborators

• Chongqing Precision Biotech Co., Ltd: collaborator
• The Children's Hospital of Zhejiang University School of Medicine: lead

Study Sites (1)

Children's Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310052, China

Location

Related Publications (7)

• 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.

  PMID: 36109639 RESULT

• 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.

  PMID: 31974366 RESULT

• 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.

  PMID: 30842314 RESULT

• 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.

  PMID: 32472023 RESULT

• 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.

  PMID: 34347960 RESULT

• 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.

  PMID: 30592986 RESULT

• 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.

  PMID: 28925994 RESULT

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Jianhua Mao, MD

  Children's Hospital, Zhejiang University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 4, 2024
• First Posted: January 25, 2024
• Study Start: February 10, 2024
• Primary Completion: April 4, 2025
• Study Completion (Estimated): December 30, 2026
• Last Updated: February 4, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)