RecruitingPhase 1Phase 2NCT06350110

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

Sponsor

Essen Biotech

Enrollment

75 participants

Start Date

Jul 10, 2024

Study Type

INTERVENTIONAL

Conditions

Systemic Lupus Erythematosus Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Sjogren's Syndrome Autoimmune Diseases Idiopathic Inflammatory Myopathies Systemic Sclerosis Lupus Nephritis Granulomatous Polyangiitis Microscopic Polyangiitis

Summary

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.

Eligibility

Min Age: 18 YearsMax Age: 90 Years

Inclusion Criteria14

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 Criteria17

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.

Interventions

BIOLOGICALCD19- BCMA CAR-T cells

The intervention in this clinical trial involves a novel approach using CD19/BCMA-Chimeric Antigen Receptor T (CAR T) cells combined with chemotherapy. The goal is to assess safety and efficacy in patients with specific hematologic malignancies. Treatment Regimen: Patients in the trial will undergo the following regimen: Fludarabine Phosphate (Days -4 to -2): IV administration of fludarabine phosphate over 30 minutes on days -4 to -2. It's part of the preparatory regimen to enhance the body's response to CAR T-cell therapy. Cyclophosphamide (Day -2): IV cyclophosphamide over 60 minutes on day -2. CD19/BCMA-Chimeric Antigen Receptor T Cells (Day 0): IV administration of investigational therapy, CD19/BCMA-CAR T cells, over 10-20 minutes on day 0. Additional Doses: Eligible patients responding well to the initial CD19/BCMA-CAR T cell infusion without unacceptable side effects and sufficient CAR T cell availability may receive 2 or 3 additional doses.