The Safety and Efficacy of Anti-CD19 CAR-T Cells in Patients With Relapsed/Refractory Autoimmune Diseases

NCT06420154 | Not Yet Recruiting Early Phase 1

• 1 other identifier: CD19-CN-A4
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is an investigator-initiated trial to evaluate the safety and efficacy of anti- CD19-CAR-T cells in the relapse or refractory autoimmune diseases.

Conditions

Systemic Lupus Erythematosus (SLE); Sjogren's Syndrome; Systemic Sclerosis; Inflammatory Myopathy; ANCA Associated Vasculitis; Antiphospholipid Syndrome

Keywords

CAR T; CD19; Autoimmune Diseases

Outcome Measures

Primary Outcomes (3)

• Incidence of dose-limiting toxicity

  Percentage of patients receiving CAR-T cells who experience dose-limiting toxicities (DLTs).

  Up to 28 days from CAR-T infusion

• Laboratory abnormalities and type, frequency and severity of adverse events

  Safety assessments are conducted using the NCI-CTCAE version 5.0 standards (CRS and neurotoxicity will be graded according to ASTCT/ ASBMT grading criteria)

  Up to1 year from CAR-T infusion

• Proportion of patients for whom a CAR-T cell product could be prepared

  Percentage of subjects for whom the desired dose of anti-CD19 -CAR-T cells can be successfully manufactured

  Up to 4 days from apheresis

Study Arms (1)

Treatment group

EXPERIMENTAL

Biological: anti-CD19-CAR-T cells

Interventions

anti-CD19-CAR-T cells BIOLOGICAL

The subjects received infusions of anti-CD19 CAR-T cells following completion of lymphodepleting preconditioning chemotherapy. Dosage：1×10\^5 cells/Kg; 3×10\^5 cells/Kg; 1×10\^6 cells/Kg frequency：single infusion

Treatment group

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 clinical research. The person or legal guardian fully understands and informs the research and signs the informed consent form (ICF), and is willing to follow and complete all trial procedures;
• Aged 18-65 years old;
• ECOG score ≤ 2 points;
• Expected survival period is at least 12 weeks;
• Have good intravenous access (for apheresis) and have no other contraindications to blood cell separation;
• When screening patients, laboratory tests must meet the following requirements and they must not have received cell growth factors within 7 days before screening hematology assessment (long-acting colony-stimulating factor (G-CSF/PEG-CSF) requires an interval of 2 weeks):
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• Absolute neutrophil count ≥1.0×10\^9/L;
• Hemoglobin ≥60 g/L (without red blood cell transfusion within 14 days);
• Platelets ≥50×10\^9/L;
• Absolute lymphocytes (ALC) ≥ 0.5×10\^9/L;
• Serum total bilirubin ≤1.5×upper limit of normal (ULN);
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN;
• Creatinine \<1.5×ULN and endogenous creatinine clearance ≥60 mL/min. 7. The cardiac ejection fraction is ≥45%, echocardiography (ECHO) confirms that there is no pericardial effusion (except for a small amount or physiological), and the electrocardiogram results have no clinical significance; 8. Baseline oxygen saturation \>92% under non-oxygenation conditions; 9. Women of childbearing age must have a negative serum or urine pregnancy test report (women who have undergone surgical sterilization or women who are at least 2 years postmenopausal are not considered women of childbearing potential).

You may not qualify if:

• Have active central nervous system diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving the central nervous system;
• Fungal, bacterial, viral or other infections exist or are suspected and are not controlled or require intravenous antibiotic treatment; simple urinary tract infections and uncomplicated bacterial pharyngitis are allowed;
• Suffering from hepatitis B (hepatitis B virus surface antigen and hepatitis B DNA \>1000 copies/ml) or hepatitis C (positive hepatitis C antibody test); syphilis infection (antibody positive); human immunodeficiency virus (HIV) infection;
• Past medication:
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• CD19 targeted therapy;
• Inject live vaccines within 4 weeks before enrollment;
• Immunosuppressive antibodies (such as anti-CD20, anti-tumor necrosis factor, anti-interleukin 6 or anti-interleukin 6 receptor) used within 4 weeks before enrollment;
• Use immunostimulatory or immune enhancer treatment (such as tacrolimus, cyclosporine, interferon-α, interferon-β, IL-2) within the 5 half-lives before apheresis;
• Have used systemic cytotoxic drugs within 2 weeks before enrollment, including daily or weekly low-dose maintenance chemotherapy (cyclophosphamide, ifosfamide, bendamustine, clotrexate or Melphalan, vincristine, etc.);
• Long-acting growth factors within 14 days before apheresis (such as pegfilgrastim) or short-acting growth factors within 5 days before apheresis or drugs used for cell mobilization (such as granulocyte colony-stimulating factor/non- Gestin, Plexafor);
• The use of pharmacological doses of corticosteroids (\>10 mg/day of prednisone or equivalent doses of other corticosteroids) and other immunosuppressive drugs must be avoided within 4 days before enrollment.
• \. Have a history of myocardial infarction, cardiac angioplasty or stent implantation, unstable angina or other clinically significant heart diseases within 12 months before enrollment; 6. History of genetic syndromes associated with bone marrow failure, such as Fanconi anemia, Kosterman syndrome, Swachmann-Diamond syndrome, etc.; 7. History of symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months before enrollment. Subjects need to take prophylactic anticoagulant drugs; 8. Have suffered from other malignant tumors in the past or at the same time (except for basal cell carcinoma of the skin, carcinoma in situ of the breast/cervix and other malignant tumors that have been effectively controlled without treatment in the past five years); 9. Use of other investigational pharmaceutical products within 30 days before screening; 10.Women of childbearing age who are pregnant or breastfeeding (because chemotherapy has potentially dangerous effects on the fetus or baby); 11.Male and female subjects who are unwilling to undergo birth control within 6 months from the signing of the informed consent form to the completion of the last administration of the study drug; 12.Any medical activity that may interfere with the evaluation of the safety or efficacy of the study; 13.According to the investigator's judgment, the subject is unlikely to complete all study visits or procedures required by the protocol, including follow-up visits or comply with the requirements for participation in the study; 14.Those who have used any CAR-T cell products or other genetically modified T cell therapies in the past.
• Comply with the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria;
• In the moderate to severe active stage of the disease, SELENA-SLEDAI score \>6;

Sponsors & Collaborators

• First Affiliated Hospital of Wenzhou Medical University: lead
• Shanghai First Song Therapeutics Co., Ltd: collaborator

Study Sites (1)

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, 325000, China

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Sjogren's Syndrome; Scleroderma, Systemic; Myositis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antiphospholipid Syndrome; Autoimmune Diseases

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Immune System Diseases; Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye Diseases; Skin Diseases; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular

Study Officials

• LI Sun, Master's

  First Affiliated Hospital of Wenzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianxin Tu, Master's

CONTACT

+86 18267726068; Lstujianxin@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chief Physician, Head of the Department of Rheumatology and Immunology, The First Affiliated Hospital of Wenzhou Medical University

Study Record Dates

• First Submitted: May 14, 2024
• First Posted: May 17, 2024
• Study Start: May 27, 2024
• Primary Completion (Estimated): May 27, 2027
• Study Completion (Estimated): May 27, 2027
• Last Updated: May 17, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)