The Clinical Study of Structurally Optimized ET019002-T Cell Therapy for Refractory/Relapsed B-Cell Malignancies
试验速览
- 阶段
- 早期 1 期
- 入组人数
- 18
- 主要终点
- Toxicity profile of ET019002T-cell treatment
研究概览
简要总结
This study is to determine the safety, including potential dose limiting toxicities, and efficiency of ET019002-T cells and the duration of in vivo survival of ET019002-T cells in patients with relapsed/refractory B-Cell Malignancies.
详细描述
ET019002-T cell therapy is a novel chimeric T-cell therapy platform that in preclinical studies, functionally matches the efficacy of CAR-T cells, but dramatically reduces the release of cytokines upon killing of target-positive tumors.The arm of the study is experimental i.v. arm:ET019002-T cells administered by intravenous (IV) infusion.The intervention is ET019002-T cells(Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET019002)-expression construct).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed B cell malignancies including: B-cell Acute Lymphoblastic Leukemia (B-ALL) and B cell lymphomas (DLBCL、FL、MZL、LPL、HCL、CLL、BL、MCL)
- •Refractory/Relapsed B cell malignancies:
- •Age 6-80 years, male or female
- •Nidus could be evaluated: minimum diameter of single nidus ≥10mm, and/or tumor cells in bone marrow ≥ 5%
- •ECOG≤2 points
- •Function of main organs or tissues were functional: Liver - ALT/AST≤3 normal upper limit, Serum total bilirubin (TBIL) ≤2 normal upper limit; Kidney - glomerular filtration rate (GFR) > 60 mL/min/1.73 m2 or serum creatinine in normal range; Lunge - carbon monoxide diffusion capacity (DLCO) or forced expiratory volume in 1s (FEV) >45% estimate; Heart - left ventricular ejection fraction (LVEF) ≥50%
- •Expecting life span ≥3 months
- •No chemotherapy, radiation therapy or immunotherapy in 2 weeks before enrollment
- •Fertile females/males consented to use contraceptives during participation of the trial
- •Patient or his/her custodia could understand and is willing to sign the written consent
排除标准
- •Pregnancy or lactation
- •Couldn't use contraceptives during participation of the trial
- •Couldn't collect enough monocyte
- •Active and/or severe infection
- •HIV infection, active Hepatitis B or Hepatitis C infection
- •Had active autoimmune disease
- •Had non-melanoma skin carcinoma (NMSC) or Carcinoma in situ (e.g. cervix, bladder, galactophore)
- •Obvious clinical encephalopathy or novel neuron function damage
- •Organ failure: Heart - upper than NYHA level III or had uncontrolled malignant arrhythmia; Liver - upper than level III of Wuhan conference classification; Kidney - kidney failure stage3 or worse
- •Using immunosuppressive drugs or adreno-cortical hormone (ACH) within two weeks of enrollment
- •Insufficient T cell number or T cell transfection rate
- •Needed urgent disease controlling due to tumor load
- •Patients had biological treatment, immunotherapy or radiation therapy within 6 weeks prior to enrollment or are currently under these treatment
- •Substance abuse or drug addiction
- •lack of compliance, communication deficit or other unaccommodated situations
研究组 & 干预措施
The low dose group
干预措施: Low dose ET019002- T Cells (Biological)
The middle dose group
干预措施: Middle dose ET019002- T Cells (Biological)
The high dose group
干预措施: High dose ET019002- T Cells (Biological)
结局指标
主要结局
Toxicity profile of ET019002T-cell treatment
时间窗: Up to 2 years.
Frequency of treatment-related adverse events that occurred at any time from the first day of infusion that are "possibly", "likely", or "definitely" related to the study, including infusion related toxicity and ET019002 T cell related toxicity. Include but not limited to: Fever, chills, nausea, vomiting, jaundice and other gastrointestinal symptoms; Fatigue, hypotension, respiratory distress; Tumor lysis syndrome; Cytokine release syndrome; Neutropenia, thrombocytopenia; Liver and kidney dysfunction. Assessed at all visits.
Maximum Tolerated Dose
时间窗: Up to 12 weeks.
A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the ET019002T-cells,which is irreversible or life threatening or CTCAE Grade 3-5.
Tmax of serum cytokine levels
时间窗: Up to 12 weeks.
Cytokins as measured by CBA-Bioplex Multiplex Immunoassays will be presented as time to peak level.
Time to baseline for serum cytokine levels
时间窗: Up to 12 weeks.
Inceases or decreases in the amout of cytokine produced compared to baseline at time points measured up to 24 weeks since dosing.
次要结局
- Rate of disease response(Up to 12 weeks.)
- Progression free survival(PFS)(Up to 2 years.)
- Time to baseline for B cell level(Up to 2 years.)