Study of Therapeutic Efficacy of Anti-CD19 CAR-T Cells in Children With Refractory Refractory AAV

NCT06508346 | Withdrawn

• 1 other identifier: 2024-IRB-0163-P-01
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is an investigator-initiated trial aimed at assessing the safety and efficacy of anti-CD19 CAR-T cells in the treatment of childhood-onset refractory ANCA-Associated Vasculitis.

Conditions

ANCA Associated Vasculitis; CAR-T Cell Therapy

Keywords

AAV; ANCA Associated Vasculitis; CAR-T cell therapy

Outcome Measures

Primary Outcomes (1)

• The safety of CAR-T cell in refractory childhood-onset ANCA-Associated Vasculitis

  The number of occurrence and proportion of adverse events and serious adverse events that occurred

  3 months and 6 months

Secondary Outcomes (5)

• The efficiency of CAR-T cell in refractory childhood-onset AAV

  3 months and 6 months

• The efficiency of CAR-T cell in refractory childhood-onset AAV

  3 months

• Cellular kinetics

  6 months

• Autoantibody detection

  24 months

• Duration of disease response (DOR)

  24 months

Interventions

anti-CD19-CAR-T cells BIOLOGICAL

Intravenous injection

Eligibility Criteria

• Age: 5 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The trial consists of two phases, Dose Exploration (Part A) and Dose Expansion (Part B). In Part A, two dose groups (0.3×10\^5/kg, 1×10\^5/kg,) are set up, starting from the low dose group to explore the safe and effective dose. If the optimal effective dose is still not explored in the highest dose group, the dose can be increased according to the situation, and the highest dose is no more than 3×10\^5/kg. Upon the completion of Part A, the optimal dose is selected by the comprehensive judgment of the investigator and the technical partner to enter into the Part B stage. with this dose , anther 3 cases are enrolled to continue to validate the safety and efficacy. A total enrollment of 9-12 patients is expected in the whole process of the trial.

You may qualify if:

• Age:5-25 years old(including threshold);
• patient \<18 years old：PVAS≥15（total 63）；≥18 years old: BVAS≥15(total 63)
• The functions of important organs are basically normal: Cardiac function: Left ventricular ejection fraction (LVEF) ≥55% with no obvious abnormality in electrocardiogram; Renal function: eGFR≥30ML/min/1.73m2； Liver function: Asparagus cochinchinensis transase (AST) and Alanine Aminotransferase (ALT)≤3.0 ULN, Total Bilirubin (TBIL) in serum ≤2.0×ULN; Lung function: No serious lung lesions, SpO2≥92%;
• Met the standards of leukapheresis or intravenous blood collection, No contraindication for cell collection;
• Negative pregnancy test for female Subjects of childbearing age, agree to take effective contraceptive measures the first year after CAR-T infusion;
• Participants or their guardians agrees to participate in the clinical trial and sign the informed consent form which indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study.

You may not qualify if:

• Received CAR T cell therapy previously;
• Central nervous system (CNS) disease: CNS neurolupus requires intervention within 60 days);
• Pulmonary hemorrhage that need for pulmonary ventilation support for more than 1 week;
• Have a history of congenital heart disease or acute myocardial infarction within 6 months prior to screening; Or severe arrhythmias (including multisource frequent supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with moderate to massive pericardial effusion, serious myocarditis, etc; Or patients with unstable vital signs who need hypertensive drugs；
• Suffer from other diseases that require long-term use of glucocorticoid or high-dose of immunosuppressive agents;
• Uncontrollable infection, or active infection that requires systemic treatment within 1 week prior to screening；
• History of organ transplantation or hematopoietic stem cell transplantation, or ≥Grade 2 GVHD within 2 weeks prior to screening；
• Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal reference value range; Or hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range; Or positive for human immunodeficiency virus (HIV) antibodies; Or syphilis test positive; Or cytomegalovirus (CMV) DNA test positive;
• Received live vaccine within 4 weeks before screening;
• Tested positive in Blood pregnancy test；
• Previous or concurrent malignancy；
• Patients who participated in other clinical study within 3 months prior to enrollment;
• Any other conditions that the investigators deem it unsuitable for the study

Sponsors & Collaborators

• The Children's Hospital of Zhejiang University School of Medicine: lead
• Children's Hospital of Chongqing Medical University: collaborator

MeSH Terms

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Condition Hierarchy (Ancestors)

Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Jianhua Mao, PhD

  The Children's Hospital of Zhejiang University School of Medicine

  PRINCIPAL INVESTIGATOR

• Mo Wang, PhD

  Children's Hospital of Chongqing Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: July 14, 2024
• First Posted: July 18, 2024
• Study Start: August 1, 2024
• Primary Completion: July 31, 2026
• Study Completion (Estimated): July 31, 2027
• Last Updated: June 16, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)