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

NCT ID: NCT06614270

Last Updated: 2025-12-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-06
• Study Completion Date: 2027-01-06

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Participant Group

Anti-CD19 IL-10/IL15 CAR-NK

Group Type: EXPERIMENTAL

Anti-CD19 IL-10/IL15 CAR-NK

Intervention Type: 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.

Interventions

Anti-CD19 IL-10/IL15 CAR-NK

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.

Intervention Type: DRUG

Eligibility Criteria

Exclusion Criteria

1. Combined with other connective tissue diseases;

2. 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.;

3. Abnormal hepatitis B or hepatitis C test indicating active infection or chronic infection, including positive HBsAg or HBcAb test and positive hepatitis C antibody;

4. Have active tuberculosis or latent tuberculosis;

5. Human immunodeficiency virus (HIV) serology positivity or known history of HIV infection;

6. 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.;

7. Patients with primary or secondary immunodeficiency;

8. IgA deficiency (<10 mg/dL) or IgG deficiency (<400 mg/dL);

9. Receiving other investigational drug treatment or participating in any other drug trial within 3 months before screening;

10. 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;

11. 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;

12. Those who have been allergic to human or murine proteins and monoclonal antibodies in the past;

13. Received live vaccine or live attenuated vaccine within 4 weeks prior to randomization;

14. 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);

15. Other conditions that the investigator considers the patient not suitable to enter the trial.

1. Localized cutaneous SSc;

2. the duration of the disease is greater than 5 years (defined as the onset of the first non-RP symptom);

3. SSc-like syndrome related to environmental factors, such as vinyl chloride, bleomycin, etc.;

4. Any history of scleroderma renal crisis;

5. intermediate- and high-risk pulmonary hypertension;

6. Active antral vasodilation.

1. drug-induced myopathy;

2. inclusion body myositis;

3. Tumor-associated myositis (myositis occurring within 2 years of diagnosis of tumor).

1. alveolar hemorrhage, requiring invasive lung ventilation, which is expected to last longer than the screening time;

2. Need for dialysis or plasmapheresis during screening;

3. Have undergone a kidney transplant.

1. Combined with liver cirrhosis;

2. Combined with aplastic anemia (AA), myelodysplastic syndrome (MDS) or other myeloproliferative disorders (MPD);

3. drug-induced thrombocytopenia;

4. Thrombotic thrombocytopenic purpura (TTP)/microthrombotic vascular disease (TMA).

1. Obstetric APS;

2. APS incorporates other CTDs;

3. APS involves the nervous system.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

the second affiliated hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jing Xue, MD.,

Role: CONTACT

Phone: +86-13758121751

Email: jingxue@zju.edu.cn

Facility Contacts

Jing Xue

Role: primary

Other Identifiers

2024-1208

Identifier Type: -

Identifier Source: org_study_id