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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of successful manufacture and expansion of the CD19/BCMA chimeric antigen receptor (CAR) T cells | satisfy the targeted dose level and meet the required release specifications outlined in the Certificate of Analysis (COA) | 60 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rhoda M Smith, Phd | Contact | +12077706670 | clinical-trials@essen-biotech.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| District One Hospital | Recruiting | Beijing | Beijing Municipality | 086-373 | China |
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| ID | Term |
|---|---|
| D001327 | Autoimmune Diseases |
| D008180 | Lupus Erythematosus, Systemic |
| D012859 | Sjogren's Syndrome |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001172 | Arthritis, Rheumatoid |
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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.
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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.
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| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D014987 | Xerostomia |
| D012466 | Salivary Gland Diseases |
| D009059 | Mouth Diseases |
| D009057 | Stomatognathic Diseases |
| D015352 | Dry Eye Syndromes |
| D007766 | Lacrimal Apparatus Diseases |
| D005128 | Eye Diseases |