An Exploratory Clinical Study of the Safety and Efficacy of Chimeric Antigen Receptor NK Cell Injections for the Treatment of Relapsed/Refractory B-cell Related Autoimmune Diseases
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 15
- 试验地点
- 3
- 主要终点
- Incidence of Dose Limiting Toxicity (DLTs)
研究概览
简要总结
A single arm, open-label pilot study is designed to determine the safety and effectiveness of CAR NK cells in patients with relapsed/refractory B-cell related autoimmune diseases.15 patients are planned to be enrolled in the dose-escalation trial . The primary objective of the study is to evaluation of the safety and feasibility of CAR NK cells for the treatment of relapsed/refractory B-cell related autoimmune diseases. The secondary objective is to evaluate the effectiveness of CAR NK cells for the treatment of relapsed/refractory B-cell related autoimmune diseases. The exploratory objective is to evaluate expansion, persistence and ability to deplete B cells of CAR NK cells in patients with relapsed/refractory B-cell related autoimmune diseases.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects voluntarily participate in this clinical study and sign the Informed Consent Form (ICF) and are willing to follow and be able to complete all trial procedures
- •Subjects disease status of enrolment: not complete response (CR) after standard treatment; moderately to severely active autoimmune diseases
- •Age: ≥ 18 years old and ≤ 70 years old, male or female
- •Subjects with estimated survival > 12 weeks
- •Adequate organs function: Serum creatinine clearance meets relevant age/sex criteria,aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN)
- •ECOG performance ≤ 2
- •Left ventricular ejection fraction (LVEF) ≥ 45%
- •Subjects have been treated with OCS in combination with an immunosuppressive or biologic agent for at least 2 weeks prior to enrollment
排除标准
- •Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, fludarabine, tozumabs), or subjects with a history of severe allergic reactions
- •Subjects with one of the following genetic syndromes: Fanconi syndrome, Kostmann syndrome, Shwachman syndrome or any of the known bone marrow failure syndromes
- •Subjects with active or uncontrolled infections requiring parenteral antimicrobials; evidence of severe active viral or bacterial infections or uncontrolled systemic fungal infections
- •Subjects with grade III or IV heart failure (NYHA classification)
- •History of epilepsy or other central nervous system (CNS) diseases
- •History of other primary malignant tumors except: cured non-melanoma skin cancer or primary cervical cancer; subjects with inactive tumors
- •Subjects with more pronounced bleeding tendencies, such as gastrointestinal bleeding, coagulation disorders, and hypersplenism
- •Subjects with unstable angina, symptomatic congestive heart failure or myocardial infarction within the last 6 months
- •Females who are pregnant, lactating, or planning a pregnancy within six months
- •Subjects who have received other clinical trial treatment within 3 months
- •Any situation judged by the investigators that may increase the risk of the subjects or interfere with the clinical trial outcome
研究组 & 干预措施
CAR NK cells
干预措施: CAR NK cells (Drug)
结局指标
主要结局
Incidence of Dose Limiting Toxicity (DLTs)
时间窗: within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion
To characterize the safety of CAR NK Cells for moderate to severe autoimmune diseases.
Treatment Emergent Adverse Events（TEAEs）
时间窗: within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion
To characterize the safety of CAR NK Cells for moderate to severe autoimmune diseases
次要结局
- Remission rate of subjects(4, 12, 24, and 52 weeks after infusion)
- Disease control rate of subjects(4, 12, 24, and 52 weeks after infusion)
研究者
YANRU WANG
Director, Department of Rheumatology and Immunology
Affiliated Hospital of Jiangsu University