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

Recruiting

• Conditions: ANCA Associated Vasculitis; CAR-T Cell Therapy

• Registration Number: NCT06508346
• Lead Sponsor: The Children's Hospital of Zhejiang University School of Medicine

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-7-14
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Inclusion Criteria:<br><br> 1. Age:5-25 years old(including threshold);<br><br> 2. Diagnosed with AAV according to the 2022EULAR/ACR AAV classification<br> criteria;despite of the Treatment with glucocorticoids (more than 1mg/kg/ day),<br> cyclophosphamide, and rituximab for at least 3 months, still cannot achieve<br> sustained response or disease recurred after response; Or use glucocorticoid<br> combined with cyclophosphamide/rituximab plus more than one of the other<br> immunosuppressants (including azathioprine, moxophenolate, methotrexate,<br> leflunomide, tacrolimus, cyclosporine, beliuzumab, etc.) =3months,still failed to<br> achieve sustained remission or relapsed after remission; Or meet the diagnostic<br> criteria for severe vasculitis, clinical routine treatment is ineffective, the<br> benefit is judged by the investigator to outweigh the risk, and the patient or<br> guardian has fully informed consent, can be considered for inclusion?<br><br> 3. patient <18 years old:PVAS=15(total 63);=18 years old: BVAS=15(total 63)<br><br> 4. The functions of important organs are basically normal: Cardiac function: Left<br> ventricular ejection fraction (LVEF) =55% with no obvious abnormality in<br> electrocardiogram; Renal function: eGFR=30ML/min/1.73m2; Liver function: Asparagus<br> cochinchinensis transase (AST) and Alanine Aminotransferase (ALT)=3.0 ULN, Total<br> Bilirubin (TBIL) in serum =2.0×ULN; Lung function: No serious lung lesions,<br> SpO2=92%;<br><br> 5. Met the standards of leukapheresis or intravenous blood collection, No<br> contraindication for cell collection;<br><br> 6. Negative pregnancy test for female Subjects of childbearing age, agree to take<br> effective contraceptive measures the first year after CAR-T infusion;<br><br> 7. Participants or their guardians agrees to participate in the clinical trial and sign<br> the informed consent form which indicating that he/she understands the purpose and<br> procedure of the clinical trial and is willing to participate in the study.<br><br>Exclusion Criteria:<br><br> 1. Received CAR T cell therapy previously;<br><br> 2. Central nervous system (CNS) disease: CNS neurolupus requires intervention within 60<br> days);<br><br> 3. Pulmonary hemorrhage that need for pulmonary ventilation support for more than 1<br> week;<br><br> 4. Have a history of congenital heart disease or acute myocardial infarction within 6<br> months prior to screening; Or severe arrhythmias (including multisource frequent<br> supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with<br> moderate to massive pericardial effusion, serious myocarditis, etc; Or patients with<br> unstable vital signs who need hypertensive drugs;<br><br> 5. Suffer from other diseases that require long-term use of glucocorticoid or high-dose<br> of immunosuppressive agents;<br><br> 6. Uncontrollable infection, or active infection that requires systemic treatment<br> within 1 week prior to screening;<br><br> 7. History of organ transplantation or hematopoietic stem cell transplantation, or<br> =Grade 2 GVHD within 2 weeks prior to screening;<br><br> 8. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive<br> and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal<br> reference value range; Or hepatitis C virus (HCV) antibody positive and peripheral<br> blood hepatitis C virus (HCV) RNA titer greater than the normal reference value<br> range; Or positive for human immunodeficiency virus (HIV) antibodies; Or syphilis<br> test positive; Or cytomegalovirus (CMV) DNA test positive;<br><br> 9. Received live vaccine within 4 weeks before screening;<br><br> 10. Tested positive in Blood pregnancy test;<br><br> 11. Previous or concurrent malignancy;<br><br> 12. Patients who participated in other clinical study within 3 months prior to<br> enrollment;<br><br> 13. Any other conditions that the investigators deem it unsuitable for the study

Exclusion Criteria

Not provided

Study & Design

• Study Type: Observational [Patient Registry]
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The safety of CAR-T cell in refractory childhood-onset ANCA-Associated Vasculitis

Secondary Outcome Measures

Name	Time	Method
The efficiency of CAR-T cell in refractory childhood-onset AAV;The efficiency of CAR-T cell in refractory childhood-onset AAV;Cellular kinetics;Autoantibody detection;Duration of disease response (DOR)