Cell Therapy with Anti-CD19 CAR-NK Cells in Patients with Relapsed or Resistant B-Acute Lymphocytic Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Incidence of dose-limiting toxicity (DLTs)
研究概览
简要总结
Immunotherapy has shown promise in treating hematological malignancies, including resistant B-ALL. One approach is CAR-NK cell therapy, which involves genetically modifying natural killer (NK) cells to target specific cancer antigens. While CAR-NK therapy offers advantages over CAR-T therapy, such as reduced immune system reactions and lower production time and cost, challenges remain regarding antitumor efficacy and the tumor microenvironment. Preclinical and early clinical studies have targeted various antigens, including CD19, with CAR-NK cells in resistant B-ALL. To further investigate the potential of anti-CD19 CAR-NK cell therapy, this study aims to evaluate its safety and determine the maximum tolerated dose (MTD) in patients who have not responded to standard treatment.
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
- 3 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Eligible diseases: Acute lymphocytic leukemia (ALL CD19+). Patients 3 years of age or older, and must have a life expectancy > 12 weeks. Eastern cooperative oncology group (ECOG) performance status of 0-2 or karnofsky performance status (KPS) score is higher than
- •Females of child-bearing potential must have a negative pregnancy test and all subjects must agree to use an effective method of contraception for up to two weeks after the last infusion of CAR NK cells.
- •Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: White blood cell count (WBC) ≥ 2500c/ml, Platelets ≥ 50×10^9/L, Hb ≥ 9.0g/dL, lymphocyte (LY) ≥ 0.7×10^9/L, LY% ≥ 15%, Alb ≥ 2.8g/dL, serum lipase and amylase < 1.5×upper limit of normal, serum creatinine ≤ 2.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal, serum total bilirubin ≤ 2.0mg/dL. These tests must be conducted within 7 days prior to registration.
- •Ability to give informed consent.
排除标准
- •Pregnant or nursing women may not participate. Active HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at the time of screening.
- •Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including active uncontrolled infection, major cardiovascular, coagulation disorders, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease, or psychiatric or emotional disorders.
- •History of severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or aldesleukin.
- •Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
- •The existence of unstable or active ulcers or gastrointestinal bleeding. Patients need anticoagulant therapy (such as warfarin or heparin). Patients need long-term antiplatelet therapy (aspirin at a dose > 300mg/d; clopidogrel at a dose > 75mg/d).
- •Patients using fludarabine or cladribine chemotherapy within 3 months prior to leukapheresis.
研究组 & 干预措施
Acute lymphocytic leukemia, in relapse
干预措施: anti CD19 CAR NK cells (Biological)
结局指标
主要结局
Incidence of dose-limiting toxicity (DLTs)
时间窗: 4 weeks
Incidence of dose-limiting toxicity (DLTs) within 4 weeks after infusion, characterized by \>= Grade 3 signs/symptoms according to CTCAE v4.03, to assess safety and tolerability.
Assessment of Maximum Tolerated Dose (MTD)
时间窗: 4 weeks
Overall Remission Rate (ORR)
时间窗: 8 weeks
Overall Remission Rate (ORR) two months after infusion, assessed using International lymphoma party (LWP) Group
次要结局
- Progression-free survival (PFS)(48 weeks)
- Duration of Response (DOR)(48 weeks)
研究者
Masoud Soleimani
Professor
Shahid Beheshti University of Medical Sciences