Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of Moderate to Severe Active SLE Clinical Research
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- MTD
研究概览
简要总结
A Study of Metabolically Armed CD19 CAR-T Cells Therapy for Patients With Moderate to Severe Active Systemic Lupus Erythematosus
详细描述
This is a single arm, open-label study. This study is indicated for moderate to severe active systemic lupus erythematosus. The selections of dose levels and the number of subjects are based on clinical trials of similar foreign products and our earlier disclosed clinical trials .
1. Main research objectives: To evaluate the safety of metabolically armed CD19 CAR-T Cells in the treatment of moderate to severe active SLE.
2. Secondary research objectives:
- To evaluate the efficacy, pharmacokinetic (PK)/pharmacodynamic (PD) characteristics, and persistence of metabolically armored CD19 CAR-T cells for moderate to severe active SLE, and their relationship with the number of B cells.
- To evaluate the effects of the concentration of autoimmune antibodies and complement after infusion of metabolically armed CD19 CAR-T Cells.
- To further explore the feasibility and safety of CAR-T therapy regimens without lymphodepletion pretreatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All subjects or guardians must sign an informed consent form approved by the Ethics Committee in person before commencing any screening process;
- •Be over 18 years of age, male or female;
- •A diagnosis of SLE according to the 2012 systemic lupus international collaborating clinics(SLICC);
- •The history of SLE prior to screening was at least 6 months, and the disease remained active at least 2 months after the use of a stable standard SLE regimen prior to screening:
- •Conventional regimens for SLE are corticosteroids and one or more immunomodulatory drugs over 6 months;
- •Oral corticosteroids must meet the following requirements:
- •Prednisone (or equivalent) ≥7.5 mg/ day, and ≤60 mg/ day;
- •There is no minimum daily dose requirement for corticosteroids when used in combination with immunosuppressants;
- •At least 8 weeks of treatment prior to screening, and the dose must be kept stable for > 2 weeks.
- •SLEDAI-2000 score ≥8 during the screening period. Score ≥6 for SLEDAI-2000 clinical symptoms (except for low complement and/or anti-DS-DNA antibodies) if low complement and/or anti-DS-DNA antibody score is present;
- •Women of childbearing age and all male patients must consent to use a effective contraception for at least 12 months after Meta10-19 infusion and until two consecutive PCR tests show no more CAR T cells in vivo;
- •CD19 expression was positive by or flow cytometry ;
- •Organ function:
- •Complete blood count (CBC) test [the following criteria should be met within 24 hours prior to apheresis, and supportive treatment such as transfusion, platelet transfusion, cell growth factor (except recombinant erythropoietin) should be avoided within 7 days prior to detection]
- •Lymphocyte count ≥ 0.5×10^9/L;
- •Platelet count ≥ 25×10^9/L;
- •Hemoglobin ≥ 70.0 g/L
- •Blood Biochemistry:
- •Serum creatinine (Scr) ≤ 1.5 x ULN, or
- •endogenous creatinine clearance ≥ 40 mL/min (using Cockcroft-Gault formula);
- •alanine aminotransferase (ALT) ≤ 2.5 x ULN;
- •aspartate aminotransferase (AST) ≤ 2.5 ×ULN;
- •Total bilirubin (TBIL) ≤ 2 ×ULN; Subjects with total bilirubin < 3 × ULN and direct bilirubin < 1.5× ULN with Gilbert-.Meulengracht syndrome could be included;
- •Serum lipase and amylase ≤ 1.5×ULN;
- •Alkaline phosphatase (ALP) ≤ 2.5 ×ULN.
- •Pulmonary function: ≤CTCAE grade 1 dyspnea and oxygen saturation of blood (SaO2) > 91% in indoor air environment..
- •Hemodynamic stability was determined by echocardiography or multichannel radionuclide angiography (MUGA) and LVEF ≥45%.
排除标准
- •Prior to screening, other lupus crises, such as active central nervous system lupus, severe myocardial damage, severe lupus pneumonia or pulmonary hemorrhage, severe lupus hepatitis, and severe vasculitis.
- •Clinically significant central nervous system diseases or pathological changes not caused by lupus prior to screening, including but not limited to: cerebrovascular accident, aneurysm, epilepsy, convulsions/convulsions, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
- •History of major organ transplantation (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation.
- •IgA deficiency was present during screening (serum IgA level < 10 mg/dL).
- •Other conditions that the investigator considered should not be enrolled in this clinical study.
研究组 & 干预措施
Administration of Metabolically Armed CD19 CAR-T cells
Patients undergo leukapheresis. Patients will receive a lymphodepletion chemotherapy with cyclophosphamide and fludarabine before CAR-T cells infusion. A dose of metabolically armed CD19 CAR-T cells will be infused on day 0.
干预措施: Metabolically Armed CD19 CAR-T cells (Drug)
结局指标
主要结局
MTD
时间窗: MTD will be determined based on DLTs observed during the first 35 days of study treatment.
Determine the Maximal Tolerable Dose(MTD).
DCR
时间窗: 3 and 6 months following infusion of Meta10-19.
Disease control rates (DCR) assessed according to SLEDAI-2000, Physician Overall Assessment (PGA), and medication.
MTD
时间窗: MTD will be determined based on Dose-limiting toxicity (DLTs) observed during the first 35 days of study treatment.
Determine the Maximal Tolerable Dose(MTD).
DLTs
时间窗: Up to 35 days after META 10-19 infusion.
Adverse events assessed according to NCI-CTCAE v5.0 criteria.
Incidence of treatment-emergent adverse events(TEAEs)
时间窗: Up to 12 months after META 10-19 infusion
To characterize the safety of META10-19 for moderate to severe active SLE.
次要结局
- Pharmacodynamics of CAR-T cells(Up to 28 days after infusion.)
- Concentration of CAR-T cells(Up to 12 months after CAR-T treatment.)
- Autoantibody detection(Up to 12 months after CAR-T treatment)
- Proportion of subjects achieving DORIS remission(on Day 28, Month 3, and Month 6 following META 10-19 infusion.)
- Proportion of subjects achieving Lupus Low Disease Activity State (LLDAS)(on Day 28, Month 3, and Month 6 following META 10-19 infusion.)
- Proportion of subjects achieving SRI-4(on Day 28, Month 3, and Month 6 following META 10-19 infusion.)
研究者
He Huang
Principal Investigator
Zhejiang University