Donor-Derived, CD19-Specific T Cell Infusion in Patients With B-Lineage Lymphoid Malignancies After Umbilical Cord Blood Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- Maximum Tolerated Dose (MTD) of T-Cell Infusions
研究概览
简要总结
The goal of this clinical research study is to learn if an infusion of white blood cells (called T cells) that have been genetically changed is safe to give patients who have received an umbilical cord blood transplant (UCBT). Researchers want to learn if these genetically changed T-cells are effective in attacking cancer cells in patients with advanced B-cell lymphoma or leukemia after they have received an UCBT, how long the changed T-cells stay in the body, and if adding them to standard transplant could improve how patients respond to treatment.
Funding Source - FDA OOPD
详细描述
T-cell infusion:
The gene transfer used in this study involves umbilical cord blood cells taken either from your UCB unit(s) or from cells left over after your UCB unit has been processed. Researchers perform a gene transfer to change the T-cells' DNA (the genetic material of cells), and then inject the changed T-cells into the body of the patient receiving the transplant. This process is called a modified donor lymphocyte infusion (DLI) or T-cell infusion.
Chemotherapy and UCBT:
After the umbilical cord blood unit has been identified for your transplant and after it has arrived at the hospital, you will be admitted to the hospital to receive chemotherapy and the UCBT. These procedures are not considered part of this research study. You will discuss these procedures with a study doctor and sign an informed consent document with specific details of the UCBT procedure and possible risks, at another time.
You will be given standard drugs to help decrease the risk of side effects. You may ask the study staff for information about how the drugs are given and their risks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 75 Years（Child, 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 primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease.
- •Patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time: 1) Acute Lymphoblastic Leukemia (ALL) with translocations 9;22 or 4;11, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure,and/or evidence of minimal residual disease; or, 2) Acute biphenotypic leukemia; or, 3) Double hit nonHodgkin's lymphoma; or, 4) Non-Hodgkin's Lymphoma (NHL) in second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant). Double hit lymphomas in first remission or more advanced disease; or, 5) Small Lymphocytic Lymphoma (SLL), or Chronic Lymphocytic Leukemia (CLL) with progressive disease following standard therapy.
- •Age 1 to 75 years old.
- •Performance score of at least 80% by Karnofsky or PS < 3 (ECOG) (age >/= 12 years), or Lansky Play-Performance Scale of at least 60% or greater (age <12 years).
- •Two Cord Blood units identified that are matched with the patient at 4/6, 5/6, or 6/6 HLA class I (serological) and II (molecular) antigens. Each cord must contain at least 1.5 x 10^7 total nucleated cells/Kg recipient body weight (pre-thaw). One Cord Blood unit may be used (in lieu of two) if it contains at least 2.5 x 10^7 total nucleated cells/Kg recipient body weight (pre-thaw).
- •Have identified a back up cells source in case of engraftment failure. The source can be autologous, related or unrelated.
- •Cardiac Function: left ventricular ejection fraction >/= 40%.
- •Pulmonary function: forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLCO) >/= 50% of expected, corrected for hemoglobin. For children </= 7 years of age who are unable to perform pulmonary function testing (PFT), oxygen saturation >/= 92% on room air by pulse oximetry.
- •Renal function: Serum creatinine </= 1.8mg/dl or </= 2 x upper limit of normal or creatinine clearance greater or equal than 40 cc/min. Creatinine for pediatric patients </=1.5 mg/dl or </=2 times upper limit of normal for age (whichever is less).
- •Liver function: Bilirubin </= 1.5 mg/dl or </= 4 x upper limit of normal (unless Gilbert's syndrome), ALT or AST </= 200 IU/ml or </= 5 x upper limit of normal for adults unless related to underline disease. For pediatric patients conjugated (direct) bilirubin < 2x upper limit of normal, ALT or AST < 5 times upper limit of normal.
- •Negative Beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization and willing to use an effective contraceptive measure while on study.
- •Patient or patient's legal representative, parent(s) or guardian able to provide written informed consent. Assent of a minor if participant's age is at least seven and less than eighteen years.
- •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 HCG in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or breast-feeding.
- •Patients with known allergy to bovine or murine products.
- •Patients with known history of HIV/AIDS.
- •Patients with chronic active hepatitis or cirrhosis. If positive hepatitis serology, the Study Chair may deem the patient eligible based on the results of liver biopsy.
- •Patients positive for West Nile Virus or RPR.
- •If in the opinion of PI or designee, the research participant has a significant active medical illness or condition deemed to potentially impact negatively on trial participation.
研究组 & 干预措施
Double Umbilical Cord Blood (UCB)
Infusion of CD19-specific T cells derived from cord blood (CB) 42 days following stem cell transplantation.
Starting dose level of T-cells not to exceed 106/m2.
The investigational component of the treatment plan of this study is the infusion of CD19-specific T cells derived from cord blood (CB) to be infused Day +42 to Day +100 following stem cell transplantation. The transplant component of the treatment plan will include CB transplant regimens that are commonly use for CB transplantation.
干预措施: T-Cell Infusion (Genetic)
Double Umbilical Cord Blood (UCB)
Infusion of CD19-specific T cells derived from cord blood (CB) 42 days following stem cell transplantation.
Starting dose level of T-cells not to exceed 106/m2.
The investigational component of the treatment plan of this study is the infusion of CD19-specific T cells derived from cord blood (CB) to be infused Day +42 to Day +100 following stem cell transplantation. The transplant component of the treatment plan will include CB transplant regimens that are commonly use for CB transplantation.
干预措施: Cord Blood Infusion (Procedure)
Single Umbilical Cord Blood (UCB)
Single UCB unit arm does not start enrollment until Dose Level A2 in the double UCB unit arm has been deemed safe.
Infusion of CD19-specific T cells derived from cord blood (CB) 42 days following stem cell transplantation.
Starting dose level of T-cells not to exceed 106/m2.
The investigational component of the treatment plan of this study is the infusion of CD19-specific T cells derived from cord blood (CB) to be infused Day +42 to Day +100 following stem cell transplantation. The transplant component of the treatment plan will include CB transplant regimens that are commonly use for CB transplantation
干预措施: T-Cell Infusion (Genetic)
Single Umbilical Cord Blood (UCB)
Single UCB unit arm does not start enrollment until Dose Level A2 in the double UCB unit arm has been deemed safe.
Infusion of CD19-specific T cells derived from cord blood (CB) 42 days following stem cell transplantation.
Starting dose level of T-cells not to exceed 106/m2.
The investigational component of the treatment plan of this study is the infusion of CD19-specific T cells derived from cord blood (CB) to be infused Day +42 to Day +100 following stem cell transplantation. The transplant component of the treatment plan will include CB transplant regimens that are commonly use for CB transplantation
干预措施: Cord Blood Infusion (Procedure)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of T-Cell Infusions
时间窗: 30 days following T-Cell infusion (up to 130 days)
MTD is highest dose level in which 6 participants treated with at most 2 experiencing dose-limiting toxicity (DLT) using Common Toxicity Criteria (CTC) following the t-cell infusion Day 42 to Day 100.
次要结局
- Secondary Graft Failure of T-Cell Infusions(30 days after t-cell infusion)