Anti-CD19 CAR-NK Cells in Refractory/Relapsed Systemic Lupus Erythematosus

NCT06421701 | Recruiting Phase 1

• 1 other identifier: 2024-0530
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-center, open-label, single-arm trial. The aim of this study is to investigate the safety and efficacy of anti-CD19 CAR-NK cells in patients with refractory/relapsed systemic lupus erythematosus.

Conditions

Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (1)

• The proportion of subjects with adverse events

  Incidence and severity of AEs and SAEs, including changes in laboratory values and vital signs as assessed by CTCAE v5.0.

  12 months

Secondary Outcomes (10)

• Proportion of subjects with Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response

  day 28, month 2, month 3, month 4, month 5, month 6, month 9 and month 12 after infusion.

• Proportion of participants achieving definition of remission in SLE (DORIS) remission

  day 28, month 2, month 3, month 4, month 5, month 6, month 9 and month 12 after infusion.

• Proportion of participants achieving Lupus Low Disease Activity State (LLDAS)

  day 28, month 2, month 3, month 4, month 5, month 6, month 9 and month 12 after infusion.

• Changes in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2000) score from baseline

  Within 12 months after anti-CD19 CAR-NK cell infusion

• Changes in the Physician Global Assessment (PGA) from baseline

  Within 12 months after anti-CD19 CAR-NK cell infusion

Study Arms (1)

anti-CD19 CAR-NK cells

EXPERIMENTAL

To evaluate the safety and efficacy of anti-CD19 CAR-NK cells in patients with refractory/relapsed systemic lupus erythematosus. All subjects will receive fludarabine/cyclophosphamide lymphodepletion followed by anti-CD19 CAR-NK cells infusion on Day 0, 3, and 6.

Drug: anti-CD19 CAR-NK cells

Interventions

anti-CD19 CAR-NK cells DRUG

Patients will receive Fludarabine and Cyclophosphamide for lymphodepletion conditioning. Anti-CD19 CAR-NK cells will be infused on Day 0, 3, and 6.

anti-CD19 CAR-NK cells

Eligibility Criteria

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

You may qualify if:

• Voluntarily participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up;
• Age range from 18 to 65 years old, regardless of gender;
• Fulfilling the 2019 ACR/EULAR classification criteria of SLE;
• Presence of anti-dsDNA or decreased C3/C4 levels;
• SLEDAI-2K≥8；
• Routine treatment is ineffective or the disease relapses after remission. Definition of routine treatment: use more than two drugs, including glucocorticoid (more than 1mg/kg/d), and any two or more of the following immunomodulatory drugs for more than 6 months: cyclophosphamide, mycophenolate mofetil, azathioprine, methotrexate, leflunomide, tacrolimus, ciclosporin, iguratimod, biological agents, including rituximab, belizumab, or telitacicept；
• Hemoglobin ≥ 80g/L; white blood cell count ≥ 3 × 10\^9/L；neutrophil count ≥ 1.5 × 10\^9/L; platelets ≥ 30 × 10\^9/L;
• The functions of important organs are basically normal: ALT ≤ 2 × ULN; AST ≤ 2 × ULN; eGFR ≥ 30ml/min/1.73m2; total bilirubin ≤2.0 mg/dL; cardiac function: left ventricular ejection fraction (LVEF) ≥ 50%; non-oxygenated blood oxygen saturation \>94%; prothrombin time (PT) ≤ 1.5 × ULN；international standardized ratio (INR) ≤ 1.5 × ULN；
• Females of childbearing potential must use effective contraception during the study.

You may not qualify if:

• History of severe allergy or known hypersensitivity to any of the active ingredients of the cell product；
• Pregnant (or lactating) women;
• Severe lupus nephritis (defined as serum creatinine \> 2.5 mg/dL or 221 μmol/L), treatment with hemodialysis within 8 weeks prior to screening；
• Other lupus crises, such as active central nervous system lupus, severe hemolytic anemia, severe thrombocytopenic purpura, severe agranulocytosis, severe myocardial damage, severe lupus pneumonia or pulmonary hemorrhage, severe lupus hepatitis, and severe vasculitis within 8 weeks prior to screening；
• Combined with other autoimmune diseases requiring systemic therapy except for secondary sjogren's syndrome;
• Clinically significant central nervous system diseases or pathological changes not caused by lupus prior to screening, including but not limited to: cerebrovascular accident, aneurysm, epilepsy, convulsions, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis;
• Abnormal test results for hepatitis B or C indicate the presence of an active or chronic infection, including positive HBsAg or positive HBcAb with HBV DNA levels exceeding the normal upper limit，positive hepatitis C antibody and detectable HCV RNA；positive serology for human immunodeficiency virus (HIV) or a known history of HIV infection; patients who test positive for HBsAg, have HBV DNA levels within the normal range, and are willing to reveive full-course antiviral therapy for hepatitis B are allowed to participate in this trial.
• Cytomegalovirus DNA levels in the peripheral blood exceeding the normal upper limits；
• Active or latent tuberculosis；
• Presence of uncontrollable bacterial, fungal, viral or other infections, requiring antibiotic therapy;
• Acquired and congenital immunodeficiency diseases；
• IgA deficiency;
• Other uncontrolled diseases: acute or chronic diseases that are clinically unstable or have not been effectively controlled and are not related to SLE；
• History of malignant diseases such as malignant tumors, except for adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, superficial bladder cancer, breast cancer;
• Any active skin disease that may interfere with the study assessment of SLE, including but not limited to psoriasis, dermatomyositis, systemic sclerosis, non-LE cutaneous lupus manifestations (eg, cutaneous vascular disease, periungual telangiectasia, fingertip sclerosis, rheumatoid nodules, erythema multiforme, leg ulcers) or drug-induced lupus；

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, China, 310016, China

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

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

Study Officials

• Huaxiang Wu, PhD

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  PRINCIPAL INVESTIGATOR

• Wenbin Qian, PhD

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Huaxiang Wu, PhD

CONTACT

86-13757118395; wuhx8855@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2024
• First Posted: May 20, 2024
• Study Start: August 1, 2024
• Primary Completion: August 1, 2025
• Study Completion (Estimated): May 31, 2026
• Last Updated: May 25, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)