T Cells Expressing a Fully-Human Anti-CD19 Chimeric Antigen Receptor for Treating B-cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Percentage of Enrolled Participants Who Actually Get Treated
研究概览
简要总结
Background:
The immune system fights infection and can affect cancer cells. T cells are white blood cells that are a major part of the immune system. T cells can destroy tumors. Researchers want to try to manipulate the immune system to better recognize and kill tumor cells.
Objective:
To test the safety of giving T cells expressing a novel fully-human anti-cluster of differentiation 19 (CD19) chimeric antigen receptor (CAR) to people with advanced B-cell cancer.
Eligibility:
People ages 18-73 with a B-cell cancer that has not been controlled by other therapies.
Design:
Participants will be screened with:
Physical exam
Blood and urine tests
Heart tests
Bone marrow sample taken
Scans in machines that take pictures
Participants will have apheresis. Blood is removed through a needle in an arm. T cells are removed. The rest of the blood is returned through a needle in the other arm.
The cells will be changed in a laboratory.
Participants will get 2 chemotherapy drugs over 3 days.
Two days later, participants will check into the hospital. They will get an intravenous (IV) catheter in an arm or chest vein. They will get the T cells through the IV in 1 infusion.
After this, participants will stay in the hospital for at least 9 days and stay nearby for 2 weeks. Then they will have blood tests and see a doctor.
Participants will have visits 6 visits for 1 year after the infusion. Some may have more follow-up visits.
Participants may samples taken of spinal fluid, bone marrow, and tumors.
...
详细描述
Background:
- Improved treatments for a variety of treatment-resistant B-cell malignancies including Bcell lymphomas and chronic lymphocytic leukemia (CLL), are needed.
- A particular need is development of new treatments for chemotherapy-refractory B-cell malignancies.
- T cells can be genetically modified to express chimeric antigen receptors (CARs) that specifically target malignancy-associated antigens.
- Autologous T cells genetically modified to express CARs targeting the B-cell antigen cluster of differentiation 19 (CD19) have caused complete remissions in a small number of patients with leukemia or lymphoma. These results demonstrate that anti-CD19 CAR-expressing T cells have antimalignancy activity in humans.
- The vast majority of B-cell malignancies express CD19.
- CD19 is not expressed by normal cells except for B cells.
- We have constructed a novel fully-human anti-CD19 CAR that can specifically recognize CD19-expressing target cells in vitro and eradicate CD19-expressing tumors in mice.
- This fully-human CAR targeting CD19 has not been tested in humans before.
- Possible toxicities include cytokine-associated toxicities such as fever, hypotension, and neurological toxicities. Elimination of normal B cells is probable, and unknown toxicities are also possible.
Objectives:
Primary
-Determine the safety and feasibility of administering T cells expressing a novel fully-human anti-CD19 CAR to patients with advanced B-cell malignancies.
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 73 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
LEVEL 1 - Participants Who Received 0.66x10^6 CAR T Cells Only
LEVEL 1 - participants who received - 0.66x10^6 Chimeric Antigen Receptor (CAR) T cells only
干预措施: Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptor (CAR) T cells (Biological)
LEVEL 1 Foll/by LEVEL 2-Participants Who Received - 0.66x10^6 CAR T Cells Foll/by 2x10^6 CAR T Cells
LEVEL 1 followed by LEVEL 2 - participants who received - 0.66x10^6 Chimeric Antigen Receptor (CAR) T cells followed by 2x10^6 CAR T cells
干预措施: Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptor (CAR) T cells (Biological)
LEVEL 1 Foll/by LEVEL 2-Participants Who Received - 0.66x10^6 CAR T Cells Foll/by 2x10^6 CAR T Cells
LEVEL 1 followed by LEVEL 2 - participants who received - 0.66x10^6 Chimeric Antigen Receptor (CAR) T cells followed by 2x10^6 CAR T cells
干预措施: Cyclophosphamide (Drug)
LEVEL 1 Foll/by LEVEL 2-Participants Who Received - 0.66x10^6 CAR T Cells Foll/by 2x10^6 CAR T Cells
LEVEL 1 followed by LEVEL 2 - participants who received - 0.66x10^6 Chimeric Antigen Receptor (CAR) T cells followed by 2x10^6 CAR T cells
干预措施: Fludarabine (Drug)
LEVEL 1 Foll/by LEVEL 3 - Participants Who Received 0.66x10^6 CAR T Cells Foll/by 6x10^6 CAR T Cells
LEVEL 1 followed by LEVEL 3 - participant who received - 0.66x10^6 Chimeric Antigen Receptor (CAR) T cells followed by 6x10^6 CAR T cells
干预措施: Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptor (CAR) T cells (Biological)
LEVEL 1 Foll/by LEVEL 3 - Participants Who Received 0.66x10^6 CAR T Cells Foll/by 6x10^6 CAR T Cells
LEVEL 1 followed by LEVEL 3 - participant who received - 0.66x10^6 Chimeric Antigen Receptor (CAR) T cells followed by 6x10^6 CAR T cells
干预措施: Cyclophosphamide (Drug)
LEVEL 1 Foll/by LEVEL 3 - Participants Who Received 0.66x10^6 CAR T Cells Foll/by 6x10^6 CAR T Cells
LEVEL 1 followed by LEVEL 3 - participant who received - 0.66x10^6 Chimeric Antigen Receptor (CAR) T cells followed by 6x10^6 CAR T cells
干预措施: Fludarabine (Drug)
LEVEL 2 - Participants Who Received 2x10^6 CAR T Cells Only
LEVEL 2 - participants who received - 2x10^6 Chimeric Antigen Receptor (CAR) T cells only
干预措施: Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptor (CAR) T cells (Biological)
LEVEL 2 Followed by LEVEL 3-Participants Who Received 2x10^6 CAR T Cells Foll/by 6x10^6 CAR T Cells
LEVEL 2 followed by LEVEL 3 - participants who received - 2x10^6 Chimeric Antigen Receptor (CAR) T cells followed by 6x10^6 CAR T cells
干预措施: Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptor (CAR) T cells (Biological)
LEVEL 2 Followed by LEVEL 3-Participants Who Received 2x10^6 CAR T Cells Foll/by 6x10^6 CAR T Cells
LEVEL 2 followed by LEVEL 3 - participants who received - 2x10^6 Chimeric Antigen Receptor (CAR) T cells followed by 6x10^6 CAR T cells
干预措施: Cyclophosphamide (Drug)
LEVEL 2 Followed by LEVEL 3-Participants Who Received 2x10^6 CAR T Cells Foll/by 6x10^6 CAR T Cells
LEVEL 2 followed by LEVEL 3 - participants who received - 2x10^6 Chimeric Antigen Receptor (CAR) T cells followed by 6x10^6 CAR T cells
干预措施: Fludarabine (Drug)
LEVEL 3 - Participants Who Received 6x10^6 CAR T Cells Only
LEVEL 3 - participants who received - 6x10^6 Chimeric Antigen Receptor (CAR) T cells only
干预措施: Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptor (CAR) T cells (Biological)
结局指标
主要结局
Percentage of Enrolled Participants Who Actually Get Treated
时间窗: 4-5 weeks after the first dose
Percentage of participants enrolled who received treatment with Chimeric Antigen Receptor (CAR) T cells, Fludarabine and cyclophosphamide.
次要结局
- Number of Participants With a Duration of Best Response in Months(Response duration is the time from first documentation of response, which is one month after cell infusion in all participants, until progression, initiation of off-study treatment or the last documentation on ongoing response, approx. one month -5 years.)
- Number of Participants That Had Any Grade 2, 3, 4 and 5 Adverse Events(Date treatment consent signed to date off study, approximately 49 months and 19 days.)
- Median Peak Chimeric Antigen Receptor (CAR) T Cells Level for Participants Treated(All post-infusion time-points up to at least 2 months after infusion, and CAR+ T cell analysis will continue until the CAR+ T cell level drops to undetectable levels unless a stable low level of CAR+ T cells is present at more than 3 years after infusion.)
- Number of Participants Who Had a Best Response of Complete Remission (CR), Partial Remission (PR), Stable Disease (SD), and Progressive Disease (PD)(30 days post Chimeric Antigen Receptor (CAR) T-cells up to 5 years)
- Number of Participants Who Had a Second or Third Infusion of Chimeric Antigen Receptor (CAR)+ T Cells(Participants could receive subsequent cell infusions any time 1 month after CAR T-cell infusion until 5 years after cell infusion.)
- Number of Participants Who Had Anti-Lymphoma Activity(14 days up to 5 years post cell infusion.)
- Number of Participants With Evidence of Immunogenicity of the Chimeric Antigen Receptor (CAR) T-cell Product(9 days to 6 weeks after CAR T-cell infusion)
研究者
James Kochenderfer, M.D.
Principal Investigator
National Cancer Institute (NCI)