Autoimmune Diseases, Sjogren's Syndrome, Systemic Lupus Erythematosus, Systemic Lupus Erythematosus Acute
Conditions
Keywords
Sjogren's Syndrome, Systemic Lupus Erythematosus, Autoimmune Diseases, CAR-T
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.
Interventions
BIOLOGICALBCMA/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.
Sponsors
Essen Biotech
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
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.
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
21 Years to 90 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of dose-limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD19/BCMA chimeric antigen receptor (CAR) T cells | 28 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of successful manufacture and expansion of the CD19/BCMA chimeric antigen receptor (CAR) T cells | 60 days | satisfy the targeted dose level and meet the required release specifications outlined in the Certificate of Analysis (COA) |
Countries
China
Contacts
Primary ContactRhoda M Smith, Phd
Outcome results
None listed