Anti-CD19 IL-10/IL15 CAR-NK Cells in Refractory/Relapsed Autoimmune Diseases

NCT06614270 | Recruiting

• 1 other identifier: 2024-1208
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-center, open-label, single-arm, dose-escalation trial. The aim of this study is to investigate the safety and efficacy of Anti-CD19 IL-10/IL15 CAR-NK cells in patients with refractory/relapsed autoimmune diseases, including systemic lupus erythematosus, systemic sclerosis, idiopathic inflammatory myositis, ANCA associated vasculitis, sjogren syndrome, and antiphospholipid syndrome.

Conditions

Systemic Sclerosis (SSc); ANCA Associated Vasculitis (AAV); Idiopathic Inflammatory Myopathy (IIM); Sjogren's Syndrome; Antiphospholipid Syndrome; Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (2)

• The proportion of subjects with DLT

  DLT definition is dose-limiting toxicity.

  Within 28 days after anti-CD19 CAR-NK cells infusion

• The proportion of subjects with adverse events

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

  12 months

Secondary Outcomes (6)

• Changes in SLEDAI-2K scores and the proportions of patients achieving SRI-4 response, DORIS remission, and LLDAS in systemic lupus erythematosus.

  12 months

• changes of mRSS score for systemic sclerosis

  48 weeks

• definition of improvement by IMACS for IIM

  48 weeks

• STAR score for sjogren's syndrome

  48 weeks

• BVAS for AAV

  48 weeks

Study Arms (1)

Participant Group

EXPERIMENTAL

Anti-CD19 IL-10/IL15 CAR-NK

Drug: Anti-CD19 IL-10/IL15 CAR-NK

Interventions

Anti-CD19 IL-10/IL15 CAR-NK DRUG

Patients will receive Fludarabine and Cyclophosphamide for conditioning. Multiple doses of Anti-CD19 IL-10/IL15 CAR-NK cells will be infused on Day 0, 3, and 6.

Participant Group

Eligibility Criteria

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

You may not qualify if:

• Combined with other connective tissue diseases;
• Involvement of important organs: heart (individuals with more severe heart disease, such as angina, myocardial infarction, heart failure, and arrhythmias), kidney (eGFR \< 15 ml/min/1.73m2), liver (ALT\>3×ULN, AST\>3×ULN, TBIL \>1.5×ULN), lung (FVC\<50% predicted or hemoglobin-corrected DLCO\<40% predicted), hematologic (leukocyte \< 2.5×109/L, neutrophil count \<1.0×109/L, HGB\<60g/L), etc.;
• Abnormal hepatitis B or hepatitis C test indicating active infection or chronic infection, including positive HBsAg or HBcAb test and positive hepatitis C antibody;
• Have active tuberculosis or latent tuberculosis;
• Human immunodeficiency virus (HIV) serology positivity or known history of HIV infection;
• Presence of any known serious active infection (including bacterial, viral, fungal, etc.), including those requiring hospitalization or intravenous antibiotic therapy within 4 weeks prior to screening and oral antibiotic therapy within 2 weeks prior to screening; Those who have various chronic infections and are currently receiving corresponding treatment, such as pneumocystosis, cytomegalovirus, herpes zoster, atypical mycobacteria, etc.;
• Patients with primary or secondary immunodeficiency;
• IgA deficiency (\<10 mg/dL) or IgG deficiency (\<400 mg/dL);
• Receiving other investigational drug treatment or participating in any other drug trial within 3 months before screening;
• History of documented and confirmed malignancy within 5 years prior to screening, with the exception of basal cell carcinoma of the skin or carcinoma in situ of the cervix that has been appropriately treated or resected;
• Patients who are pregnant, breastfeeding, or planning a recent pregnancy, or who are unwilling to use a reliable contraceptive method of contraception for the duration of the study;
• Those who have been allergic to human or murine proteins and monoclonal antibodies in the past;
• Received live vaccine or live attenuated vaccine within 4 weeks prior to randomization;
• Patients who are not expected to comply with the requirements of the protocol or are not expected to complete the trial as planned (such as those with psychiatric disorders, history of alcoholism, drug or other substance abuse);
• Other conditions that the investigator considers the patient not suitable to enter the trial.

Sponsors & Collaborators

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

Study Sites (1)

the second affiliated hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310005, China

RECRUITING

MeSH Terms

Conditions

Scleroderma, Systemic; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Myositis; Antiphospholipid Syndrome; Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Autoimmune Diseases; Immune System Diseases; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases

Central Study Contacts

Jing Xue, MD.,

CONTACT

+86-13758121751; jingxue@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2024
• First Posted: September 26, 2024
• Study Start: January 6, 2025
• Primary Completion: January 6, 2026
• Study Completion (Estimated): January 6, 2027
• Last Updated: December 29, 2025

Record last verified: 2025-09

Locations

CN (1)