Treatment of Relapsed and/or Chemotherapy Refractory CD33 Positive Acute Myeloid Leukemia by CART-33 (CART33)
Clinical Study of Chimeric CD(Cluster of Differentiation)33 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory Acute Myeloid Leukemias
RATIONALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells.
PURPOSE: This clinical trial is to study genetically engineered lymphocyte therapy in treating patients with CD33 positive acute myeloid leukemias that is relapsed (after stem cell transplantation or intensive chemotherapy) or refractory to further chemotherapy.
研究概览
地位
详细说明
PRIMARY OBJECTIVES:
I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD33 vector (referred to as CART-33 cells).
II. Determine duration of in vivo survival of CART-33 cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of CART-33 TCR zeta:CD137 and TCR (T-cell receptor) zeta cells over time.
SECONDARY OBJECTIVES:
I. For patients with detectable disease, measure anti-leukemia response due to CART-33 cell infusions.
II. To determine if the CD137 transgene is superior to the TCR zeta only transgene as measured by the relative engraftment levels of CART-33 TCR zeta:CD137 and TCR zeta cells over time.
III. Estimate relative trafficking of CART-33 cells in bone marrow.
IV. For patients with stored or accessible leukemia blasts, determine leukemia cell killing by CART-33 cells in vitro.
V. Determine if cellular or humoral host immunity develops against the murine anti-CD33, and assess correlation with loss of detectable CART-33 (loss of engraftment).
VI. Determine the relative subsets of CART-33 T cells (Tcm, Tem, and Treg).
OUTLINE: Patients are assigned to 1 group according to order of enrollment.
Patients receive anti-CD33-CAR (coupled with CD137 and CD3 zeta signalling domains)vector-transduced autologous T cells on days 0,1, and 2 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 13 years.
研究类型
注册 (预期的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习地点
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Beijing
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Beijing、Beijing、中国、100853
- 招聘中
- Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital, Hematological Department, Affiliated Hospital of Changzhi Medical College
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接触：
- Xuliang Shen, Dr.
- 电话号码：86-355-13015365546
- 邮箱：shenxlcyp@sohu.com
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副研究员：
- Ying Liu, Dr.
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
Male and female subjects with CD33+ acute myeloid leukemia in patients with no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (several months to < 2 year survival) with currently available therapies will be enrolled
- CD33+ acute myeloid leukemia CR can not be achieved after at least 2 prior combination chemotherapy regimens.
AML in CR(complete remission)2 or CR3 and not eligible for allogeneic SCT because of age, comorbid disease, or lack of available family member or unrelated donor.
Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval < 1 year).
Relapsed after prior autologous or allogenic SCT. AML patients with relapsed or residual disease after at least 1 prior therapy and not eligible for allogeneic SCT.
Residual disease after primary therapy and not eligible for autologous SCT
- Expected survival > 12 weeks
- Creatinine < 2.5 mg/dl
- ALT(alanine aminotransferase)/AST (aspartate aminotransferase)< 3x normal
- Bilirubin < 2.0 mg/dl
- Any relapse after prior SCT will make patient eligible regardless of other prior therapy
- Adequate venous access for apheresis, and no other contraindications for leukapheresis
- Voluntary informed consent is given
Exclusion Criteria:
Pregnant or lactating women
- The safety of this therapy on unborn children is not known
- Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
- Uncontrolled active infection
- Active hepatitis B or hepatitis C infection
- Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
- Previously treatment with any gene therapy products
- Feasibility assessment during screening demonstrates < 30% transduction of target lymphocytes, or insufficient expansion (< 5-fold) in response to CD3/CD137 costimulation
- Any uncontrolled active medical disorder that would preclude participation as outlined
- HIV infection
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：anti-CD33 CAR T cells
Patients receive anti-CD33-CAR retroviral vector-transduced autologous or donor-derived T cells on days 0,1, 2 in the absence of disease progression or unacceptable toxicity.
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genetically modified lymphocyte therapy
其他名称：
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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研究相关不良事件的发生
大体时间：直到第 24 周
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定义为 >= 3 级体征/症状、实验室毒性和临床事件）可能、很可能或肯定与研究治疗相关
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直到第 24 周
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次要结果测量
结果测量 |
大体时间 |
|---|---|
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Anti-leukemia responses to CART-33 cell infusions
大体时间：up to 24 weeks
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up to 24 weeks
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其他结果措施
结果测量 |
大体时间 |
|---|---|
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in vivo existence of CART33
大体时间：1 year
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1 year
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合作者和调查者
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
初级完成 (预期的)
研究完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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