Autologous CD19 Specific T-cell Infusion in Patients With B-cell Chronic Lymphocytic Leukemia (B-CLL)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of CD19-specific T-cells
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of T cells that can be given in combination with standard chemotherapy to patients with CLL. The safety of this combination will also be studied.
The T cells being used in this study are a type of white blood cell that will be taken from your blood and then genetically changed in a laboratory. The process of changing the DNA (the genetic material of cells) of the T cells is called a gene transfer. After the gene transfer is complete, the genetically changed T-cells will be put back into your body. These T cells may help prevent cancer cells from coming back.
详细描述
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of genetically changed T cells, based on when you joined this study. Up to 4 dose levels of T cells will be tested. Up to 3 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose of than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of T cells is found.
All participants will receive the same dose of chemotherapy.
T Cell Collection (leukapheresis or standard blood draw):
Within 30 days after you have completed the screening tests, you will have leukapheresis performed at the Apheresis Clinic at MD Anderson.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a history of B-CLL, who have received at least 2 lines of standard chemoimmunotherapy and have persistent disease.
- •Confirmed history of CD19 positivity by flow cytometry.
- •At least 8 weeks from last cytotoxic chemotherapy. Patients may continue ibrutinib or lenalidomide. These drugs will be discontinued 1 week prior to start of lymphodepleting chemotherapy.
- •Karnofsky Performance Scale > 60%.
- •Absolute lymphocyte count >100/uL.
- •Adequate hepatic function, as defined by serum glutamate pyruvate (SGPT) <3 x upper limit of normal; serum bilirubin and alkaline phosphatase <2 x upper limit of normal, or considered not clinically significant by the study doctor or designee.
- •Able to provide written informed consent.
- •18-80 years of age.
- •Patient or patient's legal representative, parent(s) or guardian able to provide written informed consent for the long-term follow-up gene therapy study.
排除标准
- •Positive beta human chorionic gonadotropin (HCG) in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or lactating females.
- •Patients with known allergy to bovine or murine products.
- •Positive serology for HIV.
- •Presence of autoimmune phenomenon (AIHA, ITP) requiring steroid therapy.
- •Presence of Grade 3 or greater toxicity from the previous treatment.
- •Concomitant use of other investigational agents (ibrutinib or lenalidomide are allowed).
研究组 & 干预措施
T-Cell Infusion + Chemotherapy
Peripheral blood mononuclear cells (PBMC) collected via venipuncture or steady state leukapheresis after enrollment. Clinically successful T-cell production defined as amount of T-cells required for dose level for which the patient is enrolled. Fludarabine 25 mg/m2 by vein on Days -5 to Day -3. Cyclophosphamide 250 mg/kg by vein on Days -5 to -3. Beginning dose of genetically modified cells is > 5x10^7/m2 but less than or equal to 5 x10^8/m2 infused on Day 0.
干预措施: Leukapheresis (Procedure)
T-Cell Infusion + Chemotherapy
Peripheral blood mononuclear cells (PBMC) collected via venipuncture or steady state leukapheresis after enrollment. Clinically successful T-cell production defined as amount of T-cells required for dose level for which the patient is enrolled. Fludarabine 25 mg/m2 by vein on Days -5 to Day -3. Cyclophosphamide 250 mg/kg by vein on Days -5 to -3. Beginning dose of genetically modified cells is > 5x10^7/m2 but less than or equal to 5 x10^8/m2 infused on Day 0.
干预措施: Fludarabine (Drug)
T-Cell Infusion + Chemotherapy
Peripheral blood mononuclear cells (PBMC) collected via venipuncture or steady state leukapheresis after enrollment. Clinically successful T-cell production defined as amount of T-cells required for dose level for which the patient is enrolled. Fludarabine 25 mg/m2 by vein on Days -5 to Day -3. Cyclophosphamide 250 mg/kg by vein on Days -5 to -3. Beginning dose of genetically modified cells is > 5x10^7/m2 but less than or equal to 5 x10^8/m2 infused on Day 0.
干预措施: Cyclophosphamide (Drug)
T-Cell Infusion + Chemotherapy
Peripheral blood mononuclear cells (PBMC) collected via venipuncture or steady state leukapheresis after enrollment. Clinically successful T-cell production defined as amount of T-cells required for dose level for which the patient is enrolled. Fludarabine 25 mg/m2 by vein on Days -5 to Day -3. Cyclophosphamide 250 mg/kg by vein on Days -5 to -3. Beginning dose of genetically modified cells is > 5x10^7/m2 but less than or equal to 5 x10^8/m2 infused on Day 0.
干预措施: T-cell Infusion (Procedure)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of CD19-specific T-cells
时间窗: 12 months
Maximum tolerated dose (MTD) defined as the highest dose for which the posterior probability of toxicity is closest to 25%. Dose limiting toxicity (DLT) defined as new adverse events of grade 3+ (CTCAE version 4) involving cardiopulmonary, gastrointestinal, hepatic (excluding albumin), neurological, or renal parameters occurring with 6 weeks of infusion that are probably or definitely related to T-cell product. The maximum acceptable toxicity rate is 25%.
次要结局
- Clinically Successful T-Cell Production(7 weeks)