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

NCT06350110 | Recruiting Phase 1 DMC

• 1 other identifier: ESBI202492
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

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.

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

Keywords

CAR-T Cell Therapy

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD19/BCMA chimeric antigen receptor (CAR) T cells

  Will be recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 at three dose levels until the maximum tolerated dose (MTD) is determined.

  28 days

Secondary Outcomes (1)

• Rate of successful manufacture and expansion of the CD19/BCMA chimeric antigen receptor (CAR) T cells

  10-14 days after apheresis or thawing of cryopreserved peripheral blood mononuclear cell

Study Arms (1)

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

EXPERIMENTAL

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.

Biological: CD19- BCMA CAR-T cells

Interventions

CD19- BCMA CAR-T cells 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.

Also known as: EB-BH2024-2

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

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Essen Biotech: lead

Study Sites (1)

District One Hospital

Beijing, Beijing Municipality, 086-373, China

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Lupus Nephritis; Autoimmune Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Scleroderma, Systemic; Myositis; Sjogren's Syndrome

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Arthritis, Rheumatoid; Arthritis; Joint Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye Diseases

Central Study Contacts

Rhoda M Smith, Phd

CONTACT

+12077706670; clinical-trials@essen-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open-label clinical trials are a category of clinical research where the masking is minimal or nonexistent. In such trials, both the participants and the researchers are fully aware of the treatment assignments, which means participants know the treatment they are receiving, and researchers are aware of each participant's treatment group.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single Group Assignment Patients enrolled in this clinical trial will receive a carefully designed treatment regimen. Prior to the infusion of CD19 and BCMA CAR-T cells, participants will undergo preconditioning chemotherapy. This chemotherapy serves to create an optimal environment for the CAR-T cell therapy to effectively target and eliminate malignant B cells. Following chemotherapy, participants will receive the infusion of CD19 and BCMA CAR-T cells. Monitoring and Follow-up: Following the CAR-T cell infusion, patients will be subjected to rigorous monitoring to assess safety and treatment response.

Study Record Dates

• First Submitted: April 1, 2024
• First Posted: April 5, 2024
• Study Start: July 10, 2024
• Primary Completion: December 10, 2025
• Study Completion: December 28, 2025
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)