Ultra-fast BCMA/CD70 CAR-T therapy for refractory lupus

Study of Ultra-Fast Autologous BCMA/CD70-Targeted Chimeric Antigen Receptor T (CAR- T) Therapy for Refractory Systemic Lupus Erythematosus

This trial will test ultra-fast BCMA/CD70 CAR-T cell therapy in adults with systemic lupus erythematosus that has not responded to standard treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Chongqing Precision Biotech Co., Ltd (Industry-sponsored)
• Drugs / interventions: beliumab, rituximab, CAR-T, methotrexate, cyclophosphamide, prednisone, belimumab
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT07318259 on ClinicalTrials.gov

What this trial studies

This phase 1, investigator-initiated interventional study gives patients autologous CAR-T cells engineered to target BCMA and CD70, produced using an ultra-fast manufacturing system that can prepare cells in about 10 minutes. Eligible adults with active, refractory SLE will undergo leukapheresis, rapid CAR-T manufacturing, lymphodepletion as required, and a single CAR-T infusion with close safety monitoring. The primary focus is on safety and tolerability, with secondary measures including changes in SLEDAI-2K disease activity, steroid-sparing effects, and laboratory markers of B cell depletion. The study is conducted at a single center with short- and medium-term clinical and laboratory follow-up.

Who should consider this trial

Good fit: Adults (≥18) diagnosed with SLE by 2019 EULAR/ACR criteria who have SLEDAI-2K ≥8 and disease refractory to high-dose glucocorticoids and at least two DMARDs, who can undergo leukapheresis and agree to required contraception and follow-up are ideal candidates.

Not a fit: Patients with mild or well-controlled SLE, those unable to undergo leukapheresis or lymphodepletion, pregnant or breastfeeding people, or those with uncontrolled infection or other contraindications to CAR-T therapy are unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could produce deep and sustained reductions in autoimmune B cells and disease activity, potentially reducing or eliminating the need for long-term immunosuppressive drugs.

How similar studies have performed: Early clinical reports since 2019 using CAR-T approaches against B cell targets in autoimmune diseases, including small SLE series, have shown promising remissions but remain limited and preliminary.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years old;
* 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), and/or 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;
* 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 until one year after CAR-T infusion;
* Participant or his/her guardians agree 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 30 days;
* 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 NYHA classification class IV; or combined with moderate to massive pericardial effusion, serious myocarditis, etc; or patient with unstable vital signs who need hypertensive drugs;
* The functions of important organs meet one of the following conditions: (1)renal function: eGFR\<30mL/min/1.73m2 or require renal replacement therapy; (2)liver function: AST and ALT\>3.0 ULN, total Bilirubin (TBIL) in serum \>2.0×ULN; (3)lung function: SpO2\<92% with no oxygen inhalation;
* Uncontrollable infection or active infection that requires systemic treatment within 3 months prior to screening;
* Received 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 active pulmonary tuberculosis at screening;
* Received live vaccine within 4 weeks prior to screening;
* Positive in blood pregnancy test;
* Suffered from malignant disease such as tumors (excluding tumors without active lesions and ending treatment for more than 5 years, as well as fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, thyroid cancer after radical resection, ductal carcinoma in situ after radical resection);
* 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

Nanjing, Jiangsu

• Affiliated Drum Tower Hospital, Medical School of Nanjing University — Nanjing, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Lingyun Sun

Conditions Systemic Lupus Erythematosus; BCMA/CD70; CAR-T