Ultra-fast autologous CD19 CAR-T therapy for refractory systemic lupus erythematosus

Study of Ultra-Fast Autologous CD19-targeted Chimeric Antigen Receptor T (CAR- T) Therapy for Refractory Systemic Lupus Erythematosus

This trial will try ultra-fast autologous CD19 CAR-T cell therapy in people aged 5 and older with moderate-to-severe SLE that has not responded to high-dose steroids and multiple immunosuppressants.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 5 Years and up
• Sex: All
• Sponsor: The Children's Hospital of Zhejiang University School of Medicine (Academic / other)
• Drugs / interventions: Beliumab, rituximab, CAR-T, methotrexate, cyclophosphamide, prednisone, belimumab
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT07233642 on ClinicalTrials.gov

What this trial studies

This single-center, investigator-initiated Phase 1 trial uses an ultra-fast manufacturing system to produce autologous CD19-targeted CAR-T cells in minutes for infusion into patients with refractory SLE. Eligible participants are age ≥5 diagnosed by the 2019 EULAR/ACR criteria with SLEDAI-2K ≥8 and persistent disease despite high-dose glucocorticoids plus hydroxychloroquine and at least two DMARDs or who are intolerant to standard treatments, and who have acceptable cardiac, renal, liver, and lung function. After leukapheresis and rapid CAR-T production, participants will receive a CD19 CAR-T infusion and be closely monitored for safety, organ function, disease activity, B cell depletion, and remission duration. The trial prioritizes safety outcomes while collecting early signals of clinical efficacy to guide larger studies.

Who should consider this trial

Good fit: Ideal candidates are patients aged ≥5 with moderate-to-severe, treatment-refractory SLE (SLEDAI-2K ≥8) who have adequate cardiac, renal, hepatic, and pulmonary function and can undergo leukapheresis.

Not a fit: Patients with mild or well-controlled SLE, severe organ failure, active serious infection, or who do not meet the refractory treatment criteria are unlikely to benefit from this early-phase therapy.

Why it matters

Potential benefit: If successful, this approach could produce durable remission and reduce or eliminate the need for lifelong immunosuppressive medications in refractory SLE.

How similar studies have performed: Early clinical reports since 2019 using CD19 CAR-T in autoimmune diseases, including small SLE cohorts, have shown promising remissions, but evidence is limited and preliminary.

Eligibility criteria

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.

Where this trial is running

Hangzhou, Zhejiang

• Children's Hospital of Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Jianhua Mao, MD — The Children's Hospital of Zhejiang University School of Medicine
• Study coordinator: Jianhua Mao, MD

Conditions Systemic Lupus Erythematosus; CD19; CAR-T