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

NCT ID: NCT06428188

Last Updated: 2024-11-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-29
• Study Completion Date: 2026-12-28

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.

Detailed Description

Chimeric antigen receptor (CAR)-modified T cells targeted against CD19 have demonstrated unprecedented successes in treating patients with hematopoietic and lymphoid malignancies. Besides CD19, many other molecules such as CD22, CD30,BCMA,CD123, etc. may have the potential to develop the corresponding CAR-T cells to treat patients whose tumors express those markers. In this study, investigators will evaluate the safety and efficacy of CAR-T targeting CD19/BCMA in patients with Autoimmune Disease. The primary goal is safety assessment including cytokine storm response and any other adverse effects. In addition, disease status after treatment will also be evaluated.

The purpose of this clinical trial is to assess the feasibility, safety, and efficacy of multiple CAR T-cell therapy that combines CAR T cells against Autoimmune Disease B Cells with CAR T cells targeting BCMA or CD19 or both in patients with relapsed and refractory Autoimmune Disease. The study also aims to learn more about the function of CAR T cells and their persistence in Autoimmune Disease patients.

Conditions

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

Study Design

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

Study Groups

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 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.

Group Type: EXPERIMENTAL

BCMA/CD19 CAR-T cells

Intervention Type: 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.

Interventions

BCMA/CD19 CAR-T cells

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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;
• Situations considered unsuitable for inclusion by other researchers.

• Minimum Eligible Age: 21 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

ESBI202497

Identifier Type: -

Identifier Source: org_study_id