An Assessment of the Safety and Feasibility of Administering T-Cells Expressing an Anti-CD19 Chimeric Antigen Receptor to Patients With B-Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Number of Participants With a Response Assessed by the Response Criteria for Malignant Lymphoma
研究概览
简要总结
Background:
The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy for treating patients with B cell lymphomas or leukemias that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with a type of virus (retrovirus) to attack only the tumor cells, and then giving the cells back to the patient. This type of therapy is called gene transfer. In this protocol, we are modifying the patient s white blood cells with a retrovirus that has the gene for anti-cluster of differentiation 19 (CD19) incorporated in the retrovirus.
Objective:
The purpose of this study is to determine a safe number of these cells to infuse and to see if these particular tumor-fighting cells (anti-CD19 cells) cause tumors to shrink.
Eligibility:
- Adults age 18-70 with B cell lymphomas or leukemias expressing the CD19 molecule.
Design:
Work up stage: Patients will be seen as an outpatient at the National Institutes of Health (NIH) clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed
Leukapheresis: If the patients meet all of the requirements for the study they will undergo leukapheresis to obtain white blood cells to make the anti-CD19 cells. Leukapheresis is a common procedure, which removes only the white blood cells from the patient.
Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy and the anti-CD19 cells. They will stay in the hospital for about 4 weeks for the treatment.
Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits will take up to 2 days.
详细描述
BACKGROUND:
- We have constructed a retroviral vector that encodes an anti-cluster of differentiation 19 (CD19) chimeric antigen receptor (CAR) that recognizes the CD19 antigen. This chimeric receptor also contains the signaling domains of cluster of differentiation 28 (CD28) and cluster of differentiation 3 (CD3)-zeta. The retroviral vector can be used to mediate genetic transfer of this CAR to T cells with high efficiency (> 50%) without the need to perform any selection.
- In co-cultures with CD19-expressing target cells, anti-CD19-CAR-transduced T-cells secreted significant amounts of interferon gamma (IFN-y) and interleukin 2 (IL-2).
- We have developed a process for cryopreserving the cell product which may lead to the ability for this product to be manufactured at a central location and shipped to other institutions for treatment of a broader patient population
OBJECTIVE:
- Primary objective:
--With the approval of amendment S, to determine the safety and feasibility of the administration of cryopreserved anti-CD19-CAR engineered peripheral blood lymphocytes with a non-myeloablative conditioning regimen in patients with Bcell lymphomas.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
0.5x10^7 cells/kg
干预措施: Cyclophosphamide (Drug)
1x10^9-1x10^10+ high dose Interleukin-2
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + cryopreserved anti-CD19-CAR PBL
干预措施: Fludarabine (Drug)
1x10^9-1x10^10+ high dose Interleukin-2
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + cryopreserved anti-CD19-CAR PBL
干预措施: Cyclophosphamide (Drug)
1x10^9-1x10^10+ high dose Interleukin-2
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + cryopreserved anti-CD19-CAR PBL
干预措施: Anti-cluster of differentiation 19 (CD19)-CAR PBL (Biological)
1x10^9-1x10^10+ high dose Interleukin-2
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + cryopreserved anti-CD19-CAR PBL
干预措施: Aldesleukin (Drug)
1x10^9-1x10^10 + high dose Retreat
干预措施: Fludarabine (Drug)
1x10^9-1x10^10 + high dose Retreat
干预措施: Cyclophosphamide (Drug)
1x10^9-1x10^10 + high dose Retreat
干预措施: Anti-cluster of differentiation 19 (CD19)-CAR PBL (Biological)
1x10^9-1x10^10 + high dose Retreat
干预措施: Aldesleukin (Drug)
0.5x10^7 cells/kg
干预措施: Fludarabine (Drug)
0.5x10^7 cells/kg
干预措施: Anti-cluster of differentiation 19 (CD19)-CAR PBL (Biological)
2.5x10^6 cells/kg
干预措施: Fludarabine (Drug)
2.5x10^6 cells/kg
干预措施: Cyclophosphamide (Drug)
2.5x10^6 cells/kg
干预措施: Anti-cluster of differentiation 19 (CD19)-CAR PBL (Biological)
1.0x10^6 cells/kg
干预措施: Fludarabine (Drug)
1.0x10^6 cells/kg
干预措施: Cyclophosphamide (Drug)
1.0x10^6 cells/kg
干预措施: Anti-cluster of differentiation 19 (CD19)-CAR PBL (Biological)
1.0x10^6 cells/kg (Reduced chemo)
干预措施: Anti-cluster of differentiation 19 (CD19)-CAR PBL (Biological)
1.0x10^6 cells/kg (Reduced chemo)
干预措施: Fludarabine (Drug)
1.0x10^6 cells/kg (Reduced chemo)
干预措施: Cyclophosphamide (Drug)
2.0x10^6 cells/kg (Reduced chemo)
干预措施: Anti-cluster of differentiation 19 (CD19)-CAR PBL (Biological)
2.0x10^6 cells/kg (Reduced chemo)
干预措施: Fludarabine (Drug)
2.0x10^6 cells/kg (Reduced chemo)
干预措施: Cyclophosphamide (Drug)
6.0x10^6 cells/kg (Reduced chemo)
干预措施: Anti-cluster of differentiation 19 (CD19)-CAR PBL (Biological)
6.0x10^6 cells/kg (Reduced chemo)
干预措施: Fludarabine (Drug)
6.0x10^6 cells/kg (Reduced chemo)
干预措施: Cyclophosphamide (Drug)
2.0x10^6 cells/kg (Moderate chemo)
干预措施: Anti-cluster of differentiation 19 (CD19)-CAR PBL (Biological)
2.0x10^6 cells/kg (Moderate chemo)
干预措施: Fludarabine (Drug)
2.0x10^6 cells/kg (Moderate chemo)
干预措施: Cyclophosphamide (Drug)
2.0x10^6 cells/kg (9-12 days culture)
干预措施: Anti-cluster of differentiation 19 (CD19)-CAR PBL (Biological)
2.0x10^6 cells/kg (9-12 days culture)
干预措施: Fludarabine (Drug)
2.0x10^6 cells/kg (9-12 days culture)
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Number of Participants With a Response Assessed by the Response Criteria for Malignant Lymphoma
时间窗: Scans performed at 6 weeks, 12 weeks and every 3-6 months for approximately 2 years
Participants were assessed by the Response Criteria for Malignant Lymphoma. Complete Remission (CR) is complete disappearance of all detectable evidence of disease and disease-related symptoms if present before therapy. Partial Remission (PR) requires ≥50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses; no increase in size of nodes, liver or spleen and no new sites of disease. Progressive disease (PD) is defined by ≥50% increase from nadir in the sum of the products of at least two lymph nodes, or if a single node is involved at least a 50% increase in the product of the diameters of this one node; and appearance of a new lesion greater than 1.5 cm in any axis even if other lesions are decreasing in size. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
次要结局
- Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v3.0).(Date treatment consent signed to date off study, approximately 101 months and 17 days.)
研究者
Steven Rosenberg, M.D.
Principal Investigator
National Cancer Institute (NCI)