A Pioneering Study on the Safety and Efficacy of CD147-Chimeric Antigen Receptor (CAR) T Cells in Patients With Relapsed or Refractory T-cell Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 早期 1 期
- 状态
- 尚未招募
- 入组人数
- 12
- 主要终点
- Maximum tolerated dose (MTD)
研究概览
简要总结
The safety and preliminary effectiveness of CD147-CAR T cells in patients with relapsed or refractory T cell non-Hodgkin's lymphoma will be investigated in this pioneering study.
详细描述
CD147 has been demonstrated higher and relatively specific expression on T cell non-Hodgkin's lymphoma. Preclinical studies have shown that CAR T cells targeting CD147 antigen can continuously eliminate Jurkat T-cell lymphoma in mice and extend survival without severe adverse events including hemolysis. Preliminary investigation of CD147-CAR T cells in solid tumors has started and shown an acceptable safety profile. The safety and preliminary effectiveness of CD147-CAR T cells in patients with relapsed or refractory T cell non-Hodgkin's lymphoma will be investigated in this pioneering study.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject must meet all of the following criteria:
- •18-65 years old;
- •Relapsed or refractory T-NHLs, including peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), ALK-positive ALCL, ALK-negative Image result for anaplastic large cell lymphoma (ALCL), enteropathy-related T-cell lymphoma, hepatosplenic T-cell lymphoma, etc.;
- •Previously received ≥2 lines of treatment without a complete response;
- •Immunohistochemical detection of tumor cells CD147 positive;
- •ECOG score 0-2;
- •The collection of mononuclear cells can be performed upon the judgment of the researcher;
- •No contraindications for allogeneic hematopoietic stem cell transplantation (AlloHCT);
- •Have donors for AlloHCT;
- •Agree for sequential treatment of AlloHCT;
- •Without serious organ dysfunction in 2 weeks before CAR-T infusion:
- •Heart: without arrhythmia, LVEF≥50%, and without pericardial effusion; without heart failure (NYHA class III or IV) within12 months before CAR-T infusion; without myocardial infarction within 12 months before CAR-T infusion; without long-QT syndrome or secondary QT interval prolongation;
- •Liver: ALT<2 times the upper limit of normal (ULN) and TBIL<1.5 times ULN, without active hepatitis;
- •APTT and PT<1.5 times ULN;
- •Kidney: Serum creatinine <1.5 mg/dl; or if the serum creatinine exceeds the upper limit, eGFR (CKD-EPI formula) needs to be > 50 ml/min;
- •Fingertip blood oxygen saturation ≥ 92%.
- •Estimated survival ≥ 3 months;
- •Sexually active patients must be willing to use an effective method of birth control during the study period and within 6 months after the study ending, and male partners should use condoms;
- •The patient is willing to join this clinical trial and sign an informed consent.
排除标准
- •Anyone who has one or more of the following:
- •A history of other malignancies with a disease-free period < 5 years (except for cured basal cell carcinoma of the skin, cured cervical carcinoma in situ, and gastrointestinal tumors proven to be cured by endoscopic mucosal resection);
- •Those who have received allogeneic hematopoietic stem cell transplantation or organ transplantation;
- •Patients with bone marrow involvement;
- •Those who are allergic to the biological agents in CAR-T cell product ;
- •Pregnant or breastfeeding;
- •Active bacterial, fungal or viral infection;
- •Receiving systemic hormone therapy 1 week before participating in the clinical trial;
- •Have received other gene therapy before;
- •HBV or HCV infection or carrier is defined as: HBsAg positive or HBV-DNA positive; anti-HCV positive and HCV-RNA positive;
- •Active HIV infection;
- •Clinical diagnosis of virus infection or uncontrolled virus activation, including cytomegalovirus (CMV), adenovirus (ADV), BK virus or human herpesvirus 6 (HHV-6), etc.;
- •Central nervous system lymphoma (CNSL) is defined as the presence of ≥5 tumor cells/ ul in cerebrospinal fluid (CSF) or MRI suggested CNSL; any other CNS diseases, such as uncontrolled epilepsy, cerebral ischemia/hemorrhage, dementia, cerebellar disease or any autoimmune disease involving the central nervous system, or received treatment for central nervous system or brain metastasis (radiotherapy, surgery or other treatments);
- •Imaging determined lung infection;
- •Inappropriate to participate in the trial with investigators' decision.
研究组 & 干预措施
Dose-escalation
Dose -1：0.1×10E+6/kg Dose 1：0.25×10E+6/kg Dose 2：0.5×10E+6/kg Dose 3：1.0×10E+6/kg Dose 4：2.0×10E+6/kg
干预措施: CD147- CAR T cells (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD)
时间窗: within 12 months
The highest dose that does not cause unacceptable side effects.
Dose-limiting toxicity (DLT)
时间窗: within 12 months
Side effects serious enough to prevent an increase in dose.
Adverse events
时间窗: within 12 months
Adverse events
Serious adverse events (SAE)
时间窗: within 12 months
Serious adverse events (SAE)
Adverse events of special interest (AESI)
时间窗: within 12 months
次要结局
- Complete response rate (CR)(At the 12th week, 6th month, 9th month and 12th month)
- Duration of response (DOR)(At the 12th week, 6th month, 9th month and 12th month)
- Overall response rate (ORR)(At the 12th week, 6th month, 9th month and 12th month)
- Cmax of CD147-CAR T cells(within 4 weeks)
- Tmax of CD147-CAR T cells(within 4 weeks)
- AUC of CD147-CAR T cells(within 4 weeks)
研究者
Xiao-Jun Huang
Prof.
Peking University People's Hospital