Clinical Study of Chimeric CD(Cluster of Differentiation)19 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory B-cell Leukemias and Lymphomas
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Occurrence of study related adverse events
研究概览
简要总结
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 studying genetically engineered lymphocyte therapy in treating patients with B-cell leukemia or lymphoma that is relapsed (after stem cell transplantation or intensive chemotherapy) or refractory to chemotherapy.
详细描述
PRIMARY OBJECTIVES:
I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD19 (cluster of differentiation antigen 19 ) vector (referred to as CART-19 cells).
II. Determine duration of in vivo survival of CART-19 cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of CART-19 TCR (T-cell receptor) zeta:CD137 and TCR zeta cells over time.
SECONDARY OBJECTIVES:
I. For patients with detectable disease, measure anti-tumor response due to CART-19 cell infusions.
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
- 5 Years 至 90 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female subjects with CD19+ B cell malignancies 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
- •CD19+ leukemia or lymphoma
- •ALL in CR2(second complete remission) or CR3(third complete remission) and not eligible for allogeneic SCT because of age, comorbid disease, or lack of available family member or unrelated donor
- •Follicular lymphoma, previously identified as CD19+:
- •At least 2 prior combination chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy
- •Stage III-IV disease
- •Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval < 1 year)
- •Disease responding or stable after most recent therapy (chemotherapy, MoAb, etc)
- •At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy. Patients with high risk disease manifested by deletion chromosome 17p will be eligible if they fail to achieve a CR to initial therapy or progress within 2 years of 1 prior
- •Less than 2 years between last chemotherapy and progression (i.e. most recent progression free interval < 2 years)
- •Not eligible or appropriate for conventional allogeneic SCT
- •Patients who achieve only a partial response to FCR(fludarabine, cyclophosphamide and Rituxan) as initial therapy will be eligible.
- •Mantle cell lymphoma:
- •Beyond 1st CR (complete remission) with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT
- •Disease responding or stable after most recent therapy (chemotherapy, MoAb, etc...)
- •Relapsed after prior autologous SCT
- •B-cell prolymphocytic leukemia (PLL) with relapsed or residual disease after at least 1 prior therapy and not eligible for allogeneic SCT
- •Diffuse large cell lymphoma, previously identified as CD19+:
- •Residual disease after primary therapy and not eligible for autologous SCT
- •Relapsed after prior autologous SCT
- •Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate of conventional allogeneic or 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 autologous 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
排除标准
- •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
结局指标
主要结局
Occurrence of study related adverse events
时间窗: Until week 24
defined as \>= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment
次要结局
- Anti-tumor responses to CART-19 cell infusions(up to 24 weeks)
研究者
Han weidong
PI
Chinese PLA General Hospital