A Single-Center, Open-Label, Non-Randomized, Single-Arm Clinical Study on the Treatment of Refractory Autoimmune Diseases With CD19-CAR T Cells
概览
- 阶段
- 1 期
- 干预措施
- CD19 CAR-T cells
- 疾病 / 适应症
- Autoimmune Diseases
- 发起方
- Beijing GoBroad Hospital
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Phase I:Dose-limiting toxicity (DLT)
- 状态
- 招募中
- 最后更新
- 上个月
概览
简要总结
The goal of this study is to evaluate the safety and effi cacy of CD19 CAR T cells in the treatment of Refractory Autoimmune Diseases.
详细描述
This is a single-center, open-label, non-randomized, Phase I/II trial. Patients with Refractory Autoimmune Diseases will receive CD19 CAR T cells. The primary objective is to learn about the safety and tolerability of CD19 CAR T cell therapy in subjects with Refractory Autoimmune Diseases and to determine the optimal biological dose (OBD) and recommend phase 2 dose (RP2D) in phase I and to learn about the efficacy CD19 CAR T-cell therapy in patients with Refractory Autoimmune Diseases in phase II. The primary endpoint is type and incidence of dose limiting toxicity (DLT) within 28 days after CD19 CAR T-cell infusion in phase I and overall response rate (ORR) in phase II. A total number of 18 subjects will be enrolled.
研究者
Jing Pan
Director of Dept of Hemato-Oncology and Immunotherapy
Beijing GoBroad Hospital
入排标准
入选标准
- •1\. Systemic lupus erythematosus (SLE) 1.
- •Refractory systemic lupus erythematosus (SLE) and / or refractory lupus nephritis (LN)
- •Male or female patients, aged 3-65 years (including 3 and 65 years);
- •Systemic lupus erythematosus that meets the 2019 American Society of Rheumatology (ACR) / European Association of Rheumatology Consortium (EULAR) classification criteria (see Annex 2);
- •Nuclear antibody (ANA) test is clearly positive, namely ANA titer 1:80 (based on the equivalent results of Hep-2 immunofluorescence or enzyme immunoassay) and / or the test at the screening visit (based on ELISA test, 30 IU / mL).
- •Refractory systemic lupus erythematosus (SLE) and / or refractory lupus nephritis (LN):
- •Patients take at least 7.5 mg of prednisolone daily to maintain low disease activity or a SLEDAI 2K score (see attachment 3) of 8 or higher.
- •Recurrence of disease activity after failure of conventional therapy or after remission. Definition of conventional treatment: using corticosteroids (1 mg / kg / day) and cyclophosphamide for 6 months; or any of the following immunomodulatory drugs for more than 3 months: antimalarial drugs, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biological agents such as rituximab, belimumab, and teacept.
- •5\) Physical strength status score (ECOG): 0-2 points; 6) The estimated survival period of 90 days; 1.
- •Immune thrombocytopenia in refractory lupus (SLE-ITP)
排除标准
- •An individual who meets any of the following criteria will be excluded from participation in this study:
- •1\. intracranial hypertension or cerebral consciousness disorder: Intracranial pressure is kept above 15mmHg; Organic encephalopathy syndrome, cerebrovascular accident, encephalitis or central nervous system vasculitis, visual impairment and other brain lesions that require intervention.
- •2\. Symptomatic heart failure or severe arrhythmia: Left ventricular ejection fraction (LVEF) \<45% within 12 months prior to screening; Abnormal electrocardiogram (ECG): left bundle branch, double bundle branch block or other clinically significant abnormal electrocardiogram; Congenital long QT interval (QT) syndrome or Fridericia correction formula (QTcF) 470 ms; Congestive heart failure (New York Heart Association Class III or IV);
- •Severe respiratory failure or other respiratory symptoms that are difficult to control:
- •Along with other types of malignant tumors;
- •Diffuse endovascular coagulation;
- •Sepsis or other infections that are difficult to control: uncontrolled active systemic bacterial, viral, fungal or parasitic infections (except nail fungal infections) or other clinically significant active diseases;
- •Uncontrolled diabetes: fasting blood glucose (FBG)≥8.0mmol/L, 2 hours postprandial blood glucose (PBG) 15 mmol/L, glycated hemoglobin (HbA 1 c) after at least 3 months of diet, exercise or related treatment; combined with diabetic ketoacidosis or other uncontrollable diabetic complications;
- •Received organ transplantation (excluding bone marrow transplantation);
- •eGFR CKD-EPI \< 30 ml/min/1.73m\^2；
研究组 & 干预措施
Experimental : CD19 CAR
Following the lymphodepleting treatment, patients will be treated with CD19 Chimeric Antigen Receptor (CAR) positive T cells as a single dose.
干预措施: CD19 CAR-T cells
结局指标
主要结局
Phase I:Dose-limiting toxicity (DLT)
时间窗: 28 days post infusion
The incidence and type of dose-limiting toxicity (DLT).
Phase I： Adverse events (AEs)
时间窗: 30 days post infusion
The incidence and severity of adverse events (AE).
Phase II: Objective response rate (ORR)
时间窗: 3 months and 6 months post infusion]
Proportions of subjects achieving Autoimmune Diseases response
次要结局
- Phase I: Objective response rate (ORR)(3 months and 6 months)
- Phase I: Long-term serious adverse events (SAEs)(From 30 days after CD19 CAR T infusion to 2 years)
- Phase I: Pharmacokinetics(PK)(Up to 2 years post infusion)
- Phase I: Pharmacodynamic(PD)(Up to 2 years post infusion)
- Phase II: Adverse events (AEs)(2 years post infusion)
- Phase II: Pharmacokinetics（PK）(Up to 2 years post infusion)
- Phase II: Pharmacodynamic(PD)(Up to 2 years post infusion)
- Phase II: Overall survival (OS)(Up to 2 years post infusion)
- Phase II:During of response (DOR)(Up to 2 years post infusion)