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

NCT ID: NCT06350110

Last Updated: 2024-10-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-10
• Study Completion Date: 2025-12-28

Brief 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.

Detailed Description

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental: Treatment (CD19/BCMA-CAR T cells, chemotherapy)

Treatment (CD19/BCMA-CAR T cells, chemotherapy)

Patients will be administered fludarabine phosphate intravenously (IV) over a 30-minute period on days -4 to -2. Additionally, cyclophosphamide will be administered intravenously (IV) over 60 minutes on day -2. Subsequently, patients will receive CD19/BCMA-CAR T cells intravenously (IV) over a duration of 10-20 minutes on day 0. Patients who exhibit positive responses to the initial dose of CD19/BCMA-CAR T cells, do not experience unacceptable side effects, and have a sufficient quantity of cells available may be eligible to receive 2 or 3 additional doses of CD19/BCMA-CAR T cells.

Group Type: EXPERIMENTAL

CD19- BCMA CAR-T cells

Intervention Type: BIOLOGICAL

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.

Interventions

CD19- 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.

Intervention Type: BIOLOGICAL

Other Intervention Names

EB-BH2024-2

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Essen Biotech

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

District One Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Rhoda M Smith, Phd

Role: CONTACT

clinical-trials@essen-biotech.com

+12077706670

Facility Contacts

SAMI XI, dr

Role: primary

SFM@districtonehospital.com

+14012275001

Other Identifiers

ESBI202492

Identifier Type: -

Identifier Source: org_study_id