NCT02710149Unknown1 期
A Clinical Research of CD20-Targeted CAR-T in B Cell Malignancies
Southwest Hospital, China1 个研究点 分布在 1 个国家目标入组 45 人开始时间: 2016年3月1日最近更新:
适应症
干预措施
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Adverse Events That Are Related to Treatment
研究概览
简要总结
The main purpose of this study is to explore the therapeutic effect of CD20-targeted chimeric antigen receptor T(CAR-T) cells in the treatment of B cell malignancies.
详细描述
The anti-CD20 antibody has been broadly used in the treatment of B cell malignancies and exhibited good clinical outcomes. The CD19-targeted CAR-T has shown exellent therapeutic efficiency in B cell malignancies,especially in acute lymphocytic leukemia. However, patients treated with CD19-targeted CAR-T may face relapse of CD19 mutation. Other targets aimed CAR-T is in need. Therefore we constructed CD20-targeted CAR-T cells and hope to start a clinicaltrial to explore the therapeutic effect of CD20-targeted CAR-T cells in the treatment of B cell malignancies.
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
- 14 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •CD20-expressing B cell malignancy must be assured and must be relapsed or refractory disease after at least one standard chemotherapy and one salvage regimen. According to current traditional therapies, there must be no available alternative curative therapies and subjects must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT, or have disease activity that prohibits SCT at this time.
- •Patients enrolled must have an evaluated score above 60 with KPS.
- •CD20 expression of the malignant cells must be detected by immunohistochemistry or by flow cytometry. In general immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood and bone marrow samples.
- •Gender is not limited, age from 14 years to 75 years.
- •Patients must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.
- •Patients are expected to survive for more than 3 months by their physicians at the time of enrollment.
- •Adequate absolute CD3 count estimated need to be assured for obtaining target cell dose based on dosage cohorts.
- •Subjects with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy:
- •CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs; CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm CNS3 with marrow disease who has failed salvage systemic and intensive IT chemotherapy (and therefore not eligible for radiation)
- •Patients with isolated CNS relapse will be eligible if they have previously been treated with cranial radiation (at least 1800 cGy).
- •Ability to give informed consent.
- •Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus.
- •Cardiac function: Left ventricular ejection fraction greater than or equal to 40% by MUGA or cardiac MRI, or fractional shortening greater than or equal to 28% by ECHO or left ventricular ejection fraction greater than or equal to 50% by ECHO.
- •Renal function: Creatinine level of peripheral blood is required no greater than 133umol/L.
- •Patients with history of allogeneic stem cell transplantation are eligible if there is no evidence of active GVHD and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
- •Patients volunteer to participate in the research.
排除标准
- •Subjects meeting any of the following criteria are not eligible for participation in the study:
- •Patients are evaluated below 60 scores with KPS.
- •Evident signs suggesting that patients are potentially allergic to cytokines.
- •Frequent infection history and recent infection is uncontrolled.
- •Patients with concomitant genetic syndrome: patients with Down syndrome, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome
- •Active acute or chronic graft-versus-host disease (GVHD) or requirement of immunosuppressant medications for GVHD within 4 weeks of enrollment.
- •Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. For additional details regarding use of steroid and immunosuppressant medications.
- •Pregnancy and nursing females.
- •HIV infection.
- •Active hepatitis B or active hepatitis C.
- •Participation in a prior investigational study within 4 weeks prior to enrollment or longer if required by local regulation. Participation in non-therapeutic research studies is allowed.
- •Class III/IV cardiovascular disability according to the New York Heart Association Classification.
- •Patients with a known history or prior diagnosis of other serious immunologic, malignant or inflammatory disease.
- •Other situations we think not eligible for participation in the research.
研究组 & 干预措施
B Cell Malignancies
Experimental
The trial will be conducted in a manner of simon two-stage design with Anti-CD20-CAR-transduced T cells, beginning in the first stage with the aim of over 30% reaction rate among 15 patients with B cell malignancies. Only when the expected reaction rate is achieved the 30 patients left can be recruited.
干预措施: Anti-CD20-CAR-transduced T cells (Biological)
结局指标
主要结局
Adverse Events That Are Related to Treatment
时间窗: 2 years
Determine the toxicity profile of the CD20 targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
次要结局
- In vivo existence of Anti-CD20 CAR-T cells(2 years)
- Reaction Rate of Treatment(2 years)
研究者
Shiqi Li
Researcher of Biotherapy Center
Southwest Hospital, China
研究点 (1)
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