RecruitingPhase 1NCT06792344

Clinical Study of CD19 CAR-T in the Treatment of Refractory Systemic Sclerosis

Clinical Study of CD19 Targeting Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of Refractory Systemic Sclerosis

Sponsor

The Children's Hospital of Zhejiang University School of Medicine

Enrollment

12 participants

Start Date

Dec 15, 2024

Study Type

INTERVENTIONAL

Conditions

Systemic Sclerosis (SSc)

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 systemic sclerosis

Eligibility

Min Age: 5 YearsMax Age: 18 Years

Inclusion Criteria8

Gender unlimited, age ≥5 years;
Meet the classification criteria for Systemic sclerosis (SSc) as defined by the 2013ACR/EULAR standards;
any one of the anti-nuclear antibodies or systemic sclerosis specific antibodies positive;
Improved Rodnan skin score (mRSS) ≥15 points (total 51 points);
Meet the definition of intractable disease: Glucocorticoids (≥0.5mg/kg/d) and cyclophosphamide, as well as one or more of the following immunomodulators (including antimalarial drugs, azathioprine,motecophanate, methotrexate, leflunomide, tachlimus, cyclosporine, and biologics including rituximab, Beliumab, and titacept, etc.), did not show significant remission of the disease for more than 3 months; Or meet the criteria for rapid disease progression , clinical routine treatment is ineffective, and the benefits outweigh the risks as determined by the investigator and the patient's or guardian's full and informed consent can be considered for inclusion.
Major organ functions were basically normal: left ventricular ejection fraction (LVEF) ≥55%, no obvious abnormality in electrocardiogram; eGFR≥30ML/min/1.73m2；AST and ALT≤3.0ULN, total bilirubin ≤2.0×ULN; SpO2≥92%, DLCO≥ 40% of predicted value, FVC≥ 50% of predicted value;
The subject of childbearing age has a negative urine pregnancy test result and agrees to take effective contraceptive measures during the test period until 1 year after the infusion;
The patient or his/her guardian agrees to participate in the clinical trial and signs an informed consent indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study

Exclusion Criteria1

（1） Severe pulmonary hypertension (PHA) (mean pulmonary pressure > 45mmHg) or other severe major organ involvement; (2) have previously received CAR T cell therapy (except those whose safety risks have been ruled out by the investigators); (3) patients with active central nervous system diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases, etc.; (4) Congenital heart disease or history of acute myocardial infarction within 6 months before screening, or severe arrhythmias (including multi-source frequent supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with a large number of pericardial effusion, serious myocarditis, etc.; Or patients with unstable vital signs who require vasoactive drugs to maintain blood pressure; (5) Active tuberculosis at the time of screening; (6) There are active infections or uncontrollable infections that require systemic treatment at the time of screening; (7) Received solid organ transplantation or hematopoietic stem cell transplantation within 3 months before screening; Acute graft-versus-host disease (GVHD) of grade 2 or above was present within 2 weeks prior to screening; (8) Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA detection greater than the normal range; Hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range; Positive for human immunodeficiency virus (HIV) antibodies; Treponema pallidum antibody positive; (9) Had received live vaccine within 4 weeks before screening; (10) Positive blood pregnancy test; (11) Patients with known malignant diseases such as tumors before screening; (12) Patients who had participated in other interventional clinical trials within 3 months before enrollment; (13) Situations in which other investigators consider it inappropriate to participate in the study

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