Fourth-gen CAR T Cells Targeting BCMA/CD19 for Refractory Systemic Lupus Erythematosus (SLE)

T-cell Infusion Targeting BCMA and CD19 for Refractory/Relapsed Systemic Lupus Erythematosus (SLE) Patients With or Without Organs Involvement

This study is a preliminary investigation, with a single-group design, not randomized and transparent, focusing on treatment. Its purpose is to identify the highest dose of BH002 injection (CD19-BCMA CAR-T cells) that patients suffering from resistant systemic lupus erythematosus can tolerate.

Systemic lupus erythematosus (SLE) is a type of autoimmune disorder characterized by the creation of autoantibody-generating immune complexes, affecting various systems and organs.

In SLE, autoreactive B cells can self-activate and morph into plasma cells that produce a high volume of autoantibodies. These cells can also expose their own antigens to autoimmune T cells, thereby stimulating T cells and leading to the release of inflammatory substances.

Conventional treatment for SLE focuses on achieving prolonged remission. In contrast, CD19-BCMA CAR-T cells offer a potential solution by eradicating the abnormal B cells responsible for antibody production. This allows for the rebuilding of the immune system and the restoration of normal immune function in patients, potentially leading to a life free from medication. This highlights the promising potential of CAR-T therapy in treating SLE.

Inclusion Criteria:

• 18-90 years old;
• Total score ≥ 10 on the EULAR/ACR 2019 SLE classification criteria.
• SELENA-SLEDAI≥8.
• Patients with CD19+ B-cell.
• Hemoglobin≥85 g/L.
• WBC≥2.5×10^9/L.
• NEUT≥1×10^9/L.
• BPC≥50×10^9/L.
• AST/ALT below 2 times the upper limit of normal; Creatinine clearance ≥30 mL/min; blood bilirubin ≤2.0 mg/dl; echocardiography indicates that the ejection fraction is ≥50%.
• Adequate venous access for apheresis, and no other contraindications for leukapheresis.
• Women of childbearing age should have a negative serum or urine pregnancy test at screening and baseline.
• Subjects agree to take effective contraceptive measures during the trial until at least 1 year after CAR-T cells infusion.
• Agree to attend follow-up visits as required.
• Voluntary participation and informed consent signed by the patient or his/her legal/authorized representative.

Exclusion Criteria:

• Renal disease: severe lupus nephritis (serum creatinine > 2.5 mg/dL or 221 μmol/L) within 8 weeks --Prior to leukapheresis, or subjects who need hemodialysis.
• CNS disease: including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident [CVA], encephalitis or CNS vasculitis, psychiatric patients with depression or suicidal thoughts.
• Patients with serious lesions and a history of present illness of vital organs such as the heart, liver,kidney blood and endocrine system.
• Patients with immunodeficiency, uncontrolled active infections and active or recurrent peptic ulcers;
• Received immunosuppressive therapy within 1 week prior to leukapheresis.
• Patients with HIV infection; Active infection of hepatitis B virus or hepatitis C virus.
• Patients with syphilis infection.
• The presence or suspicion of an active fungal, bacterial, viral or other infection that cannot be controlled during screening.
• Received live vaccine treatment within 4 weeks prior to screening.
• Severe allergies or hypersensitivity.
• Contraindication to cyclophosphamide in combination with fludarabine.
• Subjects who have undergone major surgery within 2 weeks prior to signing the informed consent form, or who are scheduled to have surgery (other than local anesthetic surgery) during the trial or within 2 weeks of the infusion.
• Cannula or drainage tubes other than central venous catheters.
• Pregnant or lactating women, or subjects who plan to have children within 1 year of treatment;
• Subjects with prior CD19 or BCMA-targeted therapy.
• Participated in any clinical study within 3 months prior to enrollment.
• Subjects with malignant tumour, except for Non-melanoma Skin Cancer with PFS>5yr; Cervical Cancer in situ; Bladder Cancer; Breast Cancer.