Study of Ultra-Fast CD19 CAR-T Therapy for Refractory SLE

Summary

This is an investigator-initiated trial aimed at assessing the safety and efficacy of ultra-fast autologous CD19-targeted CAR-T cells in the treatment of refractory systemic lupus erythematosus.

Eligibility

Inclusion Criteria:

* Age: ≥ 5 years old, and no gender limitation;
* Diagnosed with SLE according to the 2019 EULAR/ACR SLE classification criteria, and still in moderate to severe disease activity despite ≥3M of high dose glucocorticoids(prednisone≥1mg/kg/d or other equivalent amount of other steriod), hydroxychloroquine and at least 2 DMARDs(include cyclophosphamide, mycophenolate mofetil, azathioprine, methotrexate, cyclosporin, tacrolimus, sirolimus, leflunomide, telitacicept, Beliumab, and rituximab) or intolerant to standard treatments;
* SLEDAI-2K score≥8 points;
* The functions of important organs are basically normal:

  1. Cardiac function: Left ventricular ejection fraction (LVEF) ≥55% with no obvious abnormality in electrocardiogram;
  2. Renal function: eGFR≥30mL/min/1.73m2;
  3. Liver function: AST and ALT≤3.0 ULN, total Bilirubin (TBIL) in serum ≤2.0×ULN;
  4. Lung function: no serious lung lesions, SpO2≥92%;
* Meet the standards of leukapheresis or intravenous blood collection, and no contraindication for leukapheresis;
* Negative pregnancy test for female subjects of childbearing age, and 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.

Exclusion Criteria:

* Central nervous system (CNS) disease: CNS neurolupus requires intervention within 60 days);
* Severe acute nephritis: patients who have accepted or was undergoing renal replacement therapy within 3 months prior to transfusion; or in the investgator's opinion, patients who is likely to have significant kidney disease within 3 moths of the study which need high dose glucocorticoid (prednisone dose≥1mg/kg/day or equivalent amount of other steriod), cyclophosphamide, or mycophenolate mofetil treatment;
* Have a history of congenital heart disease 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;
* Uncontrollable infection, or active infection that requires systemic treatment within 3 months prior to screening;
* Received organ transplantation or hematopoietic stem cell transplantation within 3 months prior to screening, 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;
* Suffered from macrophage activation syndrome(MAS) within 1 month prior to screening (except for those whose safety risks have been ruled out by the researcher after treatment);
* Received CAR-T treatment (except for those whose safety risks have been ruled out by the researchers after treatment);
* Suffered from active pulmonary tuberculosis at screening;
* Received live vaccine within 4 weeks prior to screening;
* Positive in Blood pregnancy test;
* Previous or concurrent malignancy;
* Patients who participated in other clinical study within 3 months prior to screening;
* Any other conditions that the investigators deem it unsuitable for the study.

Conditions2

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