Universal CAR-T Cells (BRL-301) in Refractory Systemic Lupus Erythematosus
Study Details
Study Description
Brief Summary
This is an investigator initiated trial to assess the efficacy and safety of BRL-301 in the refractory systemic lupus erythematosus.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
The study had the following sequential phases: Screening, Pre-Treatment (Cell Product Preparation & Lymphodepleting Chemotherapy), Treatment and Follow-up.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: BRL-301 Allogeneic CD19-targeted Chimeric AntigenReceptor (CAR) T Cells |
Biological: BRL-301
Single dose of Allogeneic Anti-CD19 CAR T cells will be infused
Other Names:
|
Outcome Measures
Primary Outcome Measures
- The safety of BRL-301 in refractory systemic lupus erythematosus [12 months]
Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs as assessed by CTCAE v5.0.
Secondary Outcome Measures
- The efficiency of BRL-301 in refractory systemic lupus erythematosus [3 months]
Number of patients with SRI-4 response: including SELENA-SLEDAI ≥4-Point improvement, BILAG 2004 with No new A domain score AND no more than 1 new B domain scores, PGA with No worsening (<0.3-point increase)
- Cellular kinetics [12 months]
CAR transgene levels by quantitative polymerase chain reaction (qPCR) in peripheral blood
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age range from 18 to 65 years old (including threshold), regardless of gender;
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Subjects diagnosed with SLE according to the 2019 EULAR/ACR SLE classification criteria; ANA ≥ 1:80, or positive for anti dsDNA and/or anti Sm antibodies;
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Routine treatment is ineffective or the disease relapses after remission. Definition of routine treatment: use more than two drugs, including glucocorticoid (more than 1mg/kg/d) and Cyclophosphamide, and any one or more of the following immunomodulatory drugs for more than 6 months: Antimalarial medication, Azathioprine, mycophenolate mofetil, methotrexate, leflunomide, Tacrolimus, Ciclosporin, and biological agents, including rituximab, belizumab, or telitacicept
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At least one BILAG2004 Class A or two Class B score, or both;
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SELENA-SLEDAI score ≥ 8 points;
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The positive expression and expression rate of CD19 on peripheral blood B cells determined by flow cytometry;
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The functions of important organs meet the following requirements:
Bone marrow function needs to meet:
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White blood cell count ≥ 3 × 109/L;
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Neutrophil count ≥ 1 × 109/L (no Colony-stimulating factor treatment within 2 weeks before examination);
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Platelets ≥ 50 × 109/L;d. Hemoglobin ≥ 80g/L
Liver function:
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Alanine Aminotransferase (ALT) ≤ 3 × ULN;
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Asparagus cochinchinensis transase (AST) ≤ 3 × ULN;
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Total Bilirubin (TBIL) in serum ≤ 1.5 × ULN (excluding Gilbert syndrome, total bilirubin ≤ 3.0 × ULN); Renal function: Creatinine Clearance Rate (CrCl) ≥ 60 ml/minute (Cockcroft/Fault formula) ;
Coagulation function:
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International Normalized Ratio (INR) ≤ 1.5 × ULN,
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Prothrombin time (PT) ≤ 1.5 × ULN.
Cardiac function: good hemodynamic stability, left ventricular Ejection fraction (LVEF) ≥ 55%;
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Female patients of childbearing potential and male patients whose female sexual partners are of childbearing age should adopt medically recognized contraceptive measures or abstain from sex within at least 6 months after infusion of BRL-301; female patients of childbearing age should have a negative serum HCG test result within 7 days before study enrollment and be not breastfeeding;
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Willing to participate in this clinical study, sign an ICF, and complete follow-ups, with good compliance.
Exclusion Criteria:
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Have a serious history of Drug allergy or allergic constitution;
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Fungi, bacteria, viruses, or other infections that are uncontrollable or require intravenous medication treatment exist or are suspected;
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Central nervous system disease caused by SLE or not (including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident, encephalitis, central nervous system Vasculitis);
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Individuals with relatively serious heart diseases, such as angina pectoris, myocardial infarction, heart failure, and arrhythmia;
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Subjects with congenital immunoglobulin deficiency;
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Other malignant tumors (excluding non Melanoma skin cancer, cervical cancer in situ, bladder cancer cancer and breast cancer that have survived for more than 5 years without disease);
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Subjects with end-stage renal failure;
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Have received any of the following SLE treatments:
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Corticosteroid (defined as prednisone or equivalent>20 mg/day) of therapeutic dose were used before enrollment or within 72 hours before BRL-301 infusion.
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Use any other clinical study drugs for SLE within 4 weeks prior to enrollment. However, if the research treatment period is ineffective or the disease progresses, and at least 3 half-lives have passed before enrollment, enrollment is allowed.
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Had received anti CD20 monoclonal antibody (such as Rituximab) within 4 weeks before screening, tetaximab within 6 weeks, or belizumab within 12 weeks.
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Previous CAR-T cell or other genetically modified T Cell therapy.
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Subjects with positive hepatitis B B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and HBV DNA titer in peripheral blood higher than the upper limit of detection; Patients with positive hepatitis C virus (HCV) antibodies and positive peripheral blood HCV RNA; People who are positive for human immunodeficiency virus (HIV) antibodies; Those who have tested positive for syphilis;
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Having mental illness and severe cognitive impairment;
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Those who have participated in other clinical trials within the first 3 months of enrollment;
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Pregnant or intending to conceive women;
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Patients who are unsuitable for being included into this study as deemed by the investigator due to other reasons.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Bioray Laboratories
- First Affiliated Hospital of Zhejiang University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2022-BRL-301A-SLE-IIT