CD19-specific T Cell Infusion in Patients With B-Lineage Lymphoid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of T-cells ± IL-2
研究概览
简要总结
Sometimes researchers change the DNA (genetic material in cells) of donated T cells (white blood cells that support the immune system) using a process called "gene transfer." Gene transfer involves drawing blood from the patient, and then separating out the T-cells using a machine. Researchers then perform a gene transfer to change the T-cells' DNA, and then inject the changed T-cells into the body of the patient.
The goal of this clinical research study is to learn if an investigational type of gene transfer can be given reliably and safely in patients with advanced B-cell lymphoma. B cells are a type of white blood cell that fights infection and disease. Lymphoma is a type of cancer that affects the immune system, including B cells.
The gene transfer involves drawing blood, separating out T cells (white blood cells that fight infection and disease), changing the T cells' DNA (genetic material) in a specific way, and returning the changed T cells back to the body.
Researchers want to learn the highest dose of the changed T cells that can be given safely. Researchers also want to learn how long the changed T cells remain in the participant's body, and if the changed T cells can reliably treat B-cell lymphoma. Finally, researchers want to learn if interleukin-2 (IL-2) can help the changed T cells last longer in the body.
详细描述
Study Plan:
This study has 3 steps: chemotherapy, a stem cell transplant, and gene transfer. If the disease relapses (returns) during the study, you may receive the T-cell infusion without having a stem cell transplant. Your study doctor will decide if you will receive the stem cell transplant or not.
The chemotherapy combination in this study (carmustine [BiCNU®], cytarabine [Cytosar-U®], etoposide [Vepesid®], and melphalan [Alkeran®] is given to try to destroy any remaining tumor cells and prepare the body for the stem cell transplant and/or T-cell infusion.
If you receive the T cells without transplant, you may receive additional chemotherapy before the T cell infusion, if your doctor thinks it is needed. Your treating doctor will discuss these chemotherapy drugs with you, and you may sign an additional consent for those chemotherapy drugs as standard of care.
A stem cell transplant is designed to help the body attack the cancer cells that may remain after chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a history of CD19+ lymphoid malignancies that are beyond first remission or primary refractory to treatment.
- •Age 18 to 75 years.
- •Zubrod performance 0-1 or Karnofsky greater than or equal to 80%.
- •Patient able to provide written informed consent.
- •Patient able to provide written informed consent for the long-term follow-up gene therapy study.
- •Eligibility at time of transplant conditioning regimen (criteria 6-13): Zubrod performance 0-1 or Karnofsky greater than or equal to 80%.
- •Left ventricular ejection fraction >/= 40%. No uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease.
- •No symptomatic pulmonary disease. FEV1, FVC and DLCO >/= 50% of expected, corrected for hemoglobin.
- •Serum creatinine </= 1.8mg/dL or creatinine clearance >/= 40 cc/min.
- •Adequate hepatic function, as defined by SGPT <3 X upper limit of normal; serum bilirubin and alkaline phosphatase <2 X upper limit of normal, or considered not clinically significant.
- •If positive Hepatitis B and/or Hepatitis C serology, discuss with Principal Investigator or designee and consider liver biopsy.
- •No pleural/pericardial effusion or ascites estimated to be >1L.
- •Not breast feeding or pregnant. Pregnancy determined by a positive beta HCG test in a woman with child bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization.
- •Eligibility at time of T-cell infusion (criteria 14-15): No systemic corticosteroids within 3 days prior to T-cell infusion.
- •Not experiencing any new Grade >2 (CTC version 4) adverse neurologic, pulmonary, cardiac, gastrointestinal, renal or hepatic (excluding albumin) event within 24 hours prior to T-cell infusion.
- •Eligibility criteria for administration of IL-2 after T-cell infusion: Absence of new adverse event of grade >2 (CTC vs. 4) involving cardiopulmonary, hepatic (excluding albumin), gastrointestinal, neurologic, or renal toxicity probably or definitely attributed to infused T cells within one week of cells.
排除标准
- •Positive beta HCG in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
- •Patients with known allergy to bovine or murine products.
- •Positive serology for HIV.
研究组 & 干预措施
CD19-specific T cell Infusion without IL-2
Conditioning Regimen of Chemotherapy (Carmustine, Cytarabine, Etoposide, and Melphalan), Stem Cell Transplant, and Gene Transfer
Group 1 - low dose of T cells without IL-2.
Group 3 - higher dose of T cells without IL-2.
干预措施: Leukapheresis (Procedure)
CD19-specific T cell Infusion without IL-2
Conditioning Regimen of Chemotherapy (Carmustine, Cytarabine, Etoposide, and Melphalan), Stem Cell Transplant, and Gene Transfer
Group 1 - low dose of T cells without IL-2.
Group 3 - higher dose of T cells without IL-2.
干预措施: Stem Cell Transplant (Procedure)
CD19-specific T cell Infusion without IL-2
Conditioning Regimen of Chemotherapy (Carmustine, Cytarabine, Etoposide, and Melphalan), Stem Cell Transplant, and Gene Transfer
Group 1 - low dose of T cells without IL-2.
Group 3 - higher dose of T cells without IL-2.
干预措施: CD19-specific T Cell Infusion (Procedure)
CD19-specific T cell Infusion without IL-2
Conditioning Regimen of Chemotherapy (Carmustine, Cytarabine, Etoposide, and Melphalan), Stem Cell Transplant, and Gene Transfer
Group 1 - low dose of T cells without IL-2.
Group 3 - higher dose of T cells without IL-2.
干预措施: Carmustine (Drug)
CD19-specific T cell Infusion without IL-2
Conditioning Regimen of Chemotherapy (Carmustine, Cytarabine, Etoposide, and Melphalan), Stem Cell Transplant, and Gene Transfer
Group 1 - low dose of T cells without IL-2.
Group 3 - higher dose of T cells without IL-2.
干预措施: Etoposide (Drug)
CD19-specific T cell Infusion without IL-2
Conditioning Regimen of Chemotherapy (Carmustine, Cytarabine, Etoposide, and Melphalan), Stem Cell Transplant, and Gene Transfer
Group 1 - low dose of T cells without IL-2.
Group 3 - higher dose of T cells without IL-2.
干预措施: Cytarabine (Drug)
CD19-specific T cell Infusion without IL-2
Conditioning Regimen of Chemotherapy (Carmustine, Cytarabine, Etoposide, and Melphalan), Stem Cell Transplant, and Gene Transfer
Group 1 - low dose of T cells without IL-2.
Group 3 - higher dose of T cells without IL-2.
干预措施: Melphalan (Drug)
CD19-specific T cell Infusion with IL-2
Conditioning Regimen of Chemotherapy (Carmustine, Cytarabine, Etoposide, and Melphalan), Stem Cell Transplant, and Gene Transfer
Group 2 - higher dose of T cells with IL-2.
Group 4 - higher dose of T cells with IL-2.
干预措施: Leukapheresis (Procedure)
CD19-specific T cell Infusion with IL-2
Conditioning Regimen of Chemotherapy (Carmustine, Cytarabine, Etoposide, and Melphalan), Stem Cell Transplant, and Gene Transfer
Group 2 - higher dose of T cells with IL-2.
Group 4 - higher dose of T cells with IL-2.
干预措施: Stem Cell Transplant (Procedure)
CD19-specific T cell Infusion with IL-2
Conditioning Regimen of Chemotherapy (Carmustine, Cytarabine, Etoposide, and Melphalan), Stem Cell Transplant, and Gene Transfer
Group 2 - higher dose of T cells with IL-2.
Group 4 - higher dose of T cells with IL-2.
干预措施: CD19-specific T Cell Infusion (Procedure)
CD19-specific T cell Infusion with IL-2
Conditioning Regimen of Chemotherapy (Carmustine, Cytarabine, Etoposide, and Melphalan), Stem Cell Transplant, and Gene Transfer
Group 2 - higher dose of T cells with IL-2.
Group 4 - higher dose of T cells with IL-2.
干预措施: IL-2 (Drug)
CD19-specific T cell Infusion with IL-2
Conditioning Regimen of Chemotherapy (Carmustine, Cytarabine, Etoposide, and Melphalan), Stem Cell Transplant, and Gene Transfer
Group 2 - higher dose of T cells with IL-2.
Group 4 - higher dose of T cells with IL-2.
干预措施: Carmustine (Drug)
CD19-specific T cell Infusion with IL-2
Conditioning Regimen of Chemotherapy (Carmustine, Cytarabine, Etoposide, and Melphalan), Stem Cell Transplant, and Gene Transfer
Group 2 - higher dose of T cells with IL-2.
Group 4 - higher dose of T cells with IL-2.
干预措施: Etoposide (Drug)
CD19-specific T cell Infusion with IL-2
Conditioning Regimen of Chemotherapy (Carmustine, Cytarabine, Etoposide, and Melphalan), Stem Cell Transplant, and Gene Transfer
Group 2 - higher dose of T cells with IL-2.
Group 4 - higher dose of T cells with IL-2.
干预措施: Cytarabine (Drug)
CD19-specific T cell Infusion with IL-2
Conditioning Regimen of Chemotherapy (Carmustine, Cytarabine, Etoposide, and Melphalan), Stem Cell Transplant, and Gene Transfer
Group 2 - higher dose of T cells with IL-2.
Group 4 - higher dose of T cells with IL-2.
干预措施: Melphalan (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of T-cells ± IL-2
时间窗: Continuously monitored up to infusions (+14 days) then at 1 day, 3 days, 1 week, and 2 weeks after T cell infusion
The MTD is the highest dose at which at least 6 participants treated with the proportion of participants having dose limiting toxicities (DLT) \< 1/3. DLT is defined as a new adverse event of grade \>3 involving cardiopulmonary, gastrointestinal, hepatic (excluding albumin), neurological, or renal Common Terminology Criteria for Adverse Events (CTCAE) version 4 parameters that is probably or definitely related to the infused T-cell product.
次要结局
未报告次要终点