A Study to Infuse ROR1-Specific Autologous T Cells for Patients With Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Maximum Tolerated Dose (MTD) of ROR1R-CAR-T Cells for Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)
研究概览
简要总结
Gene transfer is a process in which the DNA (genetic material) of certain cells is changed. In this study, gene transfer will be performed on a type of white blood cell (called T cells) to recognize leukemia cells in the same person the T cells were collected from.
The goal of this clinical research study is to learn if it is safe to give these genetically-changed T cells back to patients with CLL/SLL. Researchers also want to learn if these cells can help to attack CLL/SLL cells.
详细描述
Standard Blood Draw or Leukapheresis (to collect T cells):
If you are found to be eligible to take part in this study, you will have T cells collected from your blood. This will be done by a standard blood draw or a procedure called leukapheresis. Your doctor will determine which is the best method is to collect your T cells.
If blood is collected through a standard blood draw, blood (less than 7 tablespoons) will be drawn over 1-2 days using one or more needle sticks in your arm.
If you are going to have leukapheresis, you may visit the Apheresis Clinic at MD Anderson. For the leukapheresis procedure, you will need to stay seated in a chair and keep both arms still for about 3 hours. Blood will be drawn from 1 arm, white blood cells will be separated from the rest of the blood cells in the leukapheresis machine, and the red cells, platelets, and plasma (liquid part of the blood) will be returned through your other arm. The leukapheresis procedure may require a total of 4-6 hours each day for up to 2 days.
Your white blood cell sample will be sent to a lab at MD Anderson so the genetically-changed T cells can be grown in the lab.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with B cell CLL/SLL, age </= 85 years old, who have active disease that meets 2008 IWCLL/NCI-WG criteria to initiate treatment.
- •Patients who have failed at least one line of a standard treatment, including bendamustine, fludarabine, ibrutinib, or alemtuzumab and require treatment within 2 years of completion of last treatment regimen or untreated patients with del17p by FISH (high-risk) who do not have an allogeneic stem cell transplant option.
- •At least 21 days from last cytotoxic chemotherapy.
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) <
- •Adequate hepatic function, defined as substance glutamate pyruvate transaminase (SGPT) <3 x upper limit of normal (ULN); serum bilirubin and alkaline phosphatase <2 x ULN, or considered not clinically significant by the study doctor or designee.
- •Adequate renal function, defined as serum creatinine <2 x ULN.
- •Able to provide written informed consent, and agree to practicing 2 forms of birth control during the study.
- •Patients must have adequate cardiac function as indicated by New York Heart Association (NYHA) classification I or II AND left ventricular ejection fraction of >40% and adequate pulmonary function as indicated by room air oxygen saturation of >94%.
排除标准
- •Surface ROR1 expression by <5% of CLL cells.
- •Positive beta-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 systemic allergy to bovine or murine products.
- •Known positive serology for human immunodeficiency virus (HIV) or human anti-mouse antibody (HAMA).
- •Active, uncontrolled autoimmune phenomenon autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura (AIHA, ITP) requiring steroid therapy.
- •Presence of >/= Grade 3 non-hematologic toxicity common terminology criteria (CTC) version 4 from the previous treatment.
- •Concurrent use of investigational therapeutic agent.
- •Prior allogeneic hematopoietic stem-cell transplantation if evidence of donor chimerism persists. Patients with exclusively autologous hematopoiesis are eligible.
- •Refusal to participate in the long-term follow-up protocol (2006-0676).
研究组 & 干预措施
ROR1R-CAR-T Cells
Peripheral blood mononuclear cells (PBMC) collected via venipuncture and/or steady state leukapheresis at discretion of PI. Participants receive a cycle of lympho-depleting chemotherapy as chosen by treating physician 4 to 5 days before ROR1R-CAR-T cell infusion : Fludarabine, Cyclophosphamide, and Rituximab (FCR), Bendamustine and Rituximab (BR), or Fludarabine, Bendamustine, and Rituximab (FBR).
Dose Escalation Cohort starting dose level of ROR1R-CAR-T cells/kg: 105 cell/kg infused via central venous catheter or by vein on Day 1.
Dose Expansion Cohort starting dose level of ROR1R-CAR-T cells/kg: MTD from Dose Escalation Cohort.
干预措施: ROR1R-CAR-T Cell Infusion (Procedure)
ROR1R-CAR-T Cells
Peripheral blood mononuclear cells (PBMC) collected via venipuncture and/or steady state leukapheresis at discretion of PI. Participants receive a cycle of lympho-depleting chemotherapy as chosen by treating physician 4 to 5 days before ROR1R-CAR-T cell infusion : Fludarabine, Cyclophosphamide, and Rituximab (FCR), Bendamustine and Rituximab (BR), or Fludarabine, Bendamustine, and Rituximab (FBR).
Dose Escalation Cohort starting dose level of ROR1R-CAR-T cells/kg: 105 cell/kg infused via central venous catheter or by vein on Day 1.
Dose Expansion Cohort starting dose level of ROR1R-CAR-T cells/kg: MTD from Dose Escalation Cohort.
干预措施: Fludarabine (Drug)
ROR1R-CAR-T Cells
Peripheral blood mononuclear cells (PBMC) collected via venipuncture and/or steady state leukapheresis at discretion of PI. Participants receive a cycle of lympho-depleting chemotherapy as chosen by treating physician 4 to 5 days before ROR1R-CAR-T cell infusion : Fludarabine, Cyclophosphamide, and Rituximab (FCR), Bendamustine and Rituximab (BR), or Fludarabine, Bendamustine, and Rituximab (FBR).
Dose Escalation Cohort starting dose level of ROR1R-CAR-T cells/kg: 105 cell/kg infused via central venous catheter or by vein on Day 1.
Dose Expansion Cohort starting dose level of ROR1R-CAR-T cells/kg: MTD from Dose Escalation Cohort.
干预措施: Cyclophosphamide (Drug)
ROR1R-CAR-T Cells
Peripheral blood mononuclear cells (PBMC) collected via venipuncture and/or steady state leukapheresis at discretion of PI. Participants receive a cycle of lympho-depleting chemotherapy as chosen by treating physician 4 to 5 days before ROR1R-CAR-T cell infusion : Fludarabine, Cyclophosphamide, and Rituximab (FCR), Bendamustine and Rituximab (BR), or Fludarabine, Bendamustine, and Rituximab (FBR).
Dose Escalation Cohort starting dose level of ROR1R-CAR-T cells/kg: 105 cell/kg infused via central venous catheter or by vein on Day 1.
Dose Expansion Cohort starting dose level of ROR1R-CAR-T cells/kg: MTD from Dose Escalation Cohort.
干预措施: Rituximab (Drug)
ROR1R-CAR-T Cells
Peripheral blood mononuclear cells (PBMC) collected via venipuncture and/or steady state leukapheresis at discretion of PI. Participants receive a cycle of lympho-depleting chemotherapy as chosen by treating physician 4 to 5 days before ROR1R-CAR-T cell infusion : Fludarabine, Cyclophosphamide, and Rituximab (FCR), Bendamustine and Rituximab (BR), or Fludarabine, Bendamustine, and Rituximab (FBR).
Dose Escalation Cohort starting dose level of ROR1R-CAR-T cells/kg: 105 cell/kg infused via central venous catheter or by vein on Day 1.
Dose Expansion Cohort starting dose level of ROR1R-CAR-T cells/kg: MTD from Dose Escalation Cohort.
干预措施: Bendamustine (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of ROR1R-CAR-T Cells for Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)
时间窗: 4 weeks
MTD defined as highest dose level in which 6 subjects have been treated with at most 1 subject experiencing ROR1R-CAR-T cell-related dose limiting toxicity (DLT). DLT defined as the following: * Common Toxicity Criteria for Adverse Effects (CTCAE) Grade ≥ 3 organ toxicity (cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic) not pre-existing or due to underlying malignancy and occurring within 30 days of study product infusion. * CTCAE Grades 3-5 allergic reactions related to study cell infusion. * CTCAE Grade ≥ 2 autoimmune reaction related to study product infusion. * Treatment-related death within 8 weeks of study product infusion.
次要结局
未报告次要终点