Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting Relapsed and Refractory CD30 Positive Lymphomas
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Number of patients with adverse events.
研究概览
简要总结
Currently, a majority of lymphomas cannot be cured by standard chemo-radiotherapy. Cluster of differentiation antigen 30 (CD30) is expressed in many lymphoma subtypes, such as Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). CD30 represents a very attractive target for chimeric antigen receptor (CAR)-based immune cell therapy. This study will evaluate a novel 4th generation CD30 CAR engineered with a self-withdrawal mechanism (FKBP-iCasp9) for both efficacy and safety evaluation in lymphoma patients.
详细描述
A large number of lymphoma patients exhaust current treatment options and die from the disease. Innovative therapy is urgently needed. Chimeric antigen receptor (CAR)-modified T cells have demonstrated unprecedented successes in treating even late stage cluster of differentiation antigen 19 (CD19) positive B cell malignancies. Besides CD19 lymphomas, many lymphomas are CD30 positive and therefore, CD30-CAR T cells may prove to be effective in treating such patients. We have developed several generations of CD30 CARs. Preclinical studies have demonstrated effective killing of CD30 target cells. In this study, two versions of CD30 CARs, both of which are 4th generation CARs with a self-withdrawal mechanism (FKBP-iCasp9), will be evaluated in CD30 lymphoma patients. The primary goal is safety assessment including cytokine storm response and any other adverse effects. In addition, tumor targeting and disease status after treatment will also be evaluated.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Relapsed or refractory CD30(+) lymphoma patients proved by immuno-histochemistry (IHC) or Flow-cytometry.
- •Not eligible for autologous stem-cell transplantation (ASCT) or relapsed after ASCT.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Pulse oximetry of > 90% on room air.
- •Adequate hepatic function, defined as alanine transaminase (ALT) <3 x upper limit of normal (ULN), aspartate aminotransferase (AST) <3 x ULN; serum bilirubin and alkaline phosphatase <2 x ULN.
- •Adequate renal function, defined as serum creatinine <2.0mg/dl.
- •Adequate heart function with LVEF≥50%
- •Measurable disease can be identified.
- •Life expectancy ≥3 months.
- •Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 1 year after the study is concluded. The male partner should use a condom.
- •Patients must sign an informed consent.
排除标准
- •Uncontrolled active infection.
- •Active infection with hepatitis B virus (HBV), hepatitis C virus (HCV).
- •HIV positive
- •Pregnant or lactating.
- •Currently enrolled in another clinical trial.
- •Concurrent use of systemic steroids.
研究组 & 干预措施
CAR T cells
Autologous 4th generation anti-CD30 CAR T cells
干预措施: Anti-CD30 CAR T cells (Genetic)
结局指标
主要结局
Number of patients with adverse events.
时间窗: 2 years.
Determine the toxicity profile of the 4th generation CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
次要结局
- Survival time of the patients.(2 years.)
- Response rates to the 4th generation CAR T cells.(2 years.)
- Survival time of Anti-CD30 CAR T cells in vivo.(2 years.)
研究者
Jun Zhu
Director
Peking University