Sequential CAR-T Cells Targeting BCMA/CD19 in Patients With Relapsed/ Refractory Autoimmune Diseases

NCT06428188 | Recruiting Phase 1 DMC

• 1 other identifier: ESBI202497
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open, single-arm, clinical study to evaluate the efficacy and safety of chimeric antigen receptor T cell immunotherapy (CAR-T) targeting BCMA or CD19 or both sequentially in the treatment of Relapsed/ Refractory Autoimmune Disease such as Sjogren's Syndrome or Systemic Lupus Erythematosus and other Autoimmune Disease.

Conditions

Autoimmune Diseases; Systemic Lupus Erythematosus; Systemic Lupus Erythematosus Acute; Sjogren's Syndrome

Keywords

Sjogren's Syndrome; Systemic Lupus Erythematosus; Autoimmune Diseases; CAR-T

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

  60 days

Study Arms (1)

CD19/BCMA-CAR T cells, chemotherapy

EXPERIMENTAL

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 BCMA/CD19 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 BCMA/CD19 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 BCMA/CD19 CAR T cells.

Biological: BCMA/CD19 CAR-T cells

Interventions

BCMA/CD19 CAR-T cells BIOLOGICAL

The intervention in this clinical trial involves a novel approach using BCMA/CD19 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. BCMA/CD19 Chimeric Antigen Receptor T Cells (Day 0): IV administration of investigational therapy, BCMA/CD19 CAR T cells, over 10-20 minutes on day 0. Additional Doses: Eligible patients responding well to the initial BCMA/CD19 CAR-T cell infusion without unacceptable side effects and sufficient CAR-T cell availability may receive 2 or 3 additional doses.

CD19/BCMA-CAR T cells, chemotherapy

Eligibility Criteria

• Age: 21 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Expected survival time ≥3 months;
• Subjects with recurrent/refractory autoimmune diseases who have failed standard treatment or lack effective treatment, Including but not limited to systemic lupus erythematosus, idiopathic inflammatory myopathy, systemic sclerosis, IGG4-associated diseases, primary Sjogren's syndrome, rheumatoid arthritis, connective tissue disease-associated interstitial lung disease, immune thrombocytopenia, primary biliary cholangitis, etc.
• Histological evidence of non-suppurative destructive cholangitis and small bile duct destruction.
• Liver and kidney function, cardiopulmonary function meet the following requirements:
• Creatinine ≤1.5×ULN; (2) Electrocardiogram showed no clinically significant abnormal bands;
• Blood oxygen saturation \>91% in non-oxygen state;
• Total bilirubin ≤2×ULN; ALT and AST≤2.5 x ULN; ALT and AST abnormalities due to disease, such as liver infiltration or bile duct obstruction, were determined to be less than 5×ULN. If Gilbert syndrome is diagnosed, the total bilirubin index can be relaxed to ≤3.0×ULN and the direct bilirubin ≤1.5×ULN.
• No serious mental disorders;
• Can understand this test and have signed the informed consent.

You may not qualify if:

• Malignant tumors other than R/R AID disease in the 5 years prior to screening, except for adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and breast ductal carcinoma in situ after radical surgery;
• Hepatitis B surface antigen (HBsAg) positive; Hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer detection is not within the normal reference value range; Hepatitis C virus (HCV) Antibody positive and peripheral blood hepatitis C virus (HCV) RNA positive; Human immunodeficiency virus (HIV) Antibody positive; Syphilis positive;
• Serious heart disease, including but not limited to unstable angina, myocardial infarction or bypass or stent surgery (within 6 months prior to screening), congestive heart failure (NYHA classification ≥III), and severe arrhythmia;
• Systemic diseases that are deemed unstable by researchers: including but not limited to severe liver, kidney, or metabolic diseases that require drug treatment;
• Active or uncontrollable infections (except mild genitourinary and upper respiratory tract infections) that require systemic treatment within 7 days prior to administration;
• Pregnant or lactating women, and female subjects who plan pregnancy within 2 years after cell transfusion or male subjects whose partners plan pregnancy within 2 years after cell transfusion;
• Patients who received CAR-T therapy or other gene-modified cell therapy before screening;
• Participated in other clinical studies 1 month before screening;
• Evidence of central nervous system invasion during subject screening;
• Mental patients with depression or suicidal thoughts;

Sponsors & Collaborators

• Essen Biotech: lead

Study Sites (1)

District One Hospital

Beijing, Beijing Municipality, 086-373, China

RECRUITING

MeSH Terms

Conditions

Autoimmune Diseases; Lupus Erythematosus, Systemic; Sjogren's Syndrome

Condition Hierarchy (Ancestors)

Immune System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal 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: Patients enrolled in this clinical trial will receive a carefully designed treatment regimen. Before the infusion of BCMA and CD19 CAR-T cells, participants will undergo preconditioning chemotherapy. This chemotherapy serves to create an optimal environment for CAR-T cell therapy to effectively target and eliminate B cells. Following chemotherapy, participants will receive the infusion of CD19 and BCMA CAR-T cells.

Study Record Dates

• First Submitted: May 20, 2024
• First Posted: May 24, 2024
• Study Start: May 29, 2024
• Primary Completion: December 10, 2025
• Study Completion (Estimated): December 28, 2026
• Last Updated: November 5, 2024

Record last verified: 2024-11

Locations

CN (1)