T Cells Expressing Fully-human Anti-CD19 and Anti-CD20 Chimeric Antigen Receptors for Treating B-cell Malignancies and Hodgkin Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Number of Participants Administered T Cells Expressing a Novel Fully- Human Anti-cluster of Differentiation 19 (CD19) and Anti-cluster of Differentiation 20 (CD20) Chimeric Antigen Receptors (CAR) Who Experienced a Dose-limiting Toxicity (DLT)
研究概览
简要总结
Background:
-Cluster of differentiation 19 (CD19) and cluster of differentiation 20 (CD20) are often found on certain cancer cells. Researchers think that a person's T cells can be modified in a lab to kill cells that have CD19 and CD20 on the surface.
Objective:
-To see if it is safe to give anti-CD19 and anti-CD20 CAR T cells to people with a B cell cancer or Hodgkin lymphoma.
Eligibility:
-People ages 18 and older with a B cell cancer or Hodgkin lymphoma that has not been controlled with standard therapies
Design:
- Participants will be screened under protocol 01C0129 with:
- Medical history
- Physical exam
- Blood and heart tests
- Bone marrow biopsy: A needle is inserted into the participant's hip bone to remove a small amount of marrow.
Scans
- Participants will have apheresis: Blood will be removed through a vein. The blood with circulate through a machine that removes the T cells. The rest of the blood will be returned to the participant.
- Once a day for 3 days before they get the T cells, participants will receive chemotherapy through a vein.
- Participants will receive the T cells through a vein. They will stay in the hospital for at least 9 days.
- Participants may have a lumbar puncture: A needle will remove fluid from the spinal cord.
- Participants may have a tumor biopsy.
- Participants will repeat the screening tests throughout the study.
- Participants will have follow-up visits 2 weeks after infusion; monthly for 4 months; at 6, 9, and 12 months; every 6 months for 3 years; and then annually for 5 years. Participants will then be contacted annually for 15 years.
详细描述
Background:
- Improved treatments for a variety of treatment-resistant malignancies including B-cell lymphomas, and chronic lymphocytic leukemia (CLL) and Hodgkin lymphoma 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 CD19 have caused complete remissions in patients with leukemia or lymphoma. These results have established anti-cluster of differentiation 19 (CD19) CAR T cells as an important therapy for relapsed lymphoma, but only about 40% of patients receiving anti-CD19 CAR T cells have durable complete remissions.
- Most B-cell malignancies express CD19 and cluster of differentiation 20 (CD20), but expression of CD19 and CD20 can be lost or diminished.
- The malignant cells of Hodgkin lymphoma, Hodgkin Reed-Sternberg cells, originate from B cells, which is the rationale for treating Hodgkin lymphoma with T cells targeting CD19 and CD20.
- CD19 and CD20 are not expressed by normal cells except for B cells and some plasma cells.
- We have constructed a novel gene therapy construct that encodes a fully-human anti-CD19 CAR with a cluster of differentiation 28 (CD28) domain and a fully-human anti-CD20 CAR with a 4-1BB (cluster of differentiation 37) domain.
- T cells expressing this CAR construct, called Hu1928-Hu20BB, can specifically recognize CD19 and CD20-expressing target cells in vitro and eradicate CD19 or CD20-expressing tumors in mice.
- One CAR expressed in this CAR construct, Hu19-CD828Z has been tested in humans before. The other CAR in the total construct, Hu20-CD8BBZ, 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 and anti-CD20 CAR construct to patients with advanced B-cell malignancies and Hodgkin lymphoma.
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 —（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
1/Conditioning chemotherapy plus Chimeric Antigen Receptors (CAR) T-cells dose escalation
All participants will be receiving escalating dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + conditioning chemotherapy
干预措施: Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells (Biological)
1/Conditioning chemotherapy plus Chimeric Antigen Receptors (CAR) T-cells dose escalation
All participants will be receiving escalating dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + conditioning chemotherapy
干预措施: Cyclophosphamide (Drug)
1/Conditioning chemotherapy plus Chimeric Antigen Receptors (CAR) T-cells dose escalation
All participants will be receiving escalating dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + conditioning chemotherapy
干预措施: Fludarabine (Drug)
2/Conditioning chemotherapy plus Chimeric Antigen Receptors (CAR) T-cells expansion phase
Maximum tolerated dose (MTD) dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + Conditioning chemotherapy
干预措施: Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells (Biological)
2/Conditioning chemotherapy plus Chimeric Antigen Receptors (CAR) T-cells expansion phase
Maximum tolerated dose (MTD) dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + Conditioning chemotherapy
干预措施: Cyclophosphamide (Drug)
2/Conditioning chemotherapy plus Chimeric Antigen Receptors (CAR) T-cells expansion phase
Maximum tolerated dose (MTD) dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + Conditioning chemotherapy
干预措施: Fludarabine (Drug)
结局指标
主要结局
Number of Participants Administered T Cells Expressing a Novel Fully- Human Anti-cluster of Differentiation 19 (CD19) and Anti-cluster of Differentiation 20 (CD20) Chimeric Antigen Receptors (CAR) Who Experienced a Dose-limiting Toxicity (DLT)
时间窗: First protocol treatment through 28 days after the CAR T-cell infusion.
A DLT are defined as toxicities assessed by the Common Terminology Criteria for Adverse Events v5.0 that are possibly, probably, or definitely attributable to protocol interventions and occurring between the first protocol treatment through 28 days after the CAR T-cell infusion.
次要结局
- Percentage of Peak Blood Chimeric Antigen Receptors (CAR) T Cells(119 days after CAR T-cell infusion)
- Percentage of Peripheral Blood Mononuclear Cells (PBMC) of Chimeric Antigen Receptors (CAR) T Cells(pretreatment and multiple days from day 1 to day 173 after infusion.)
- Last Time-Point at Which Chimeric Antigen Receptors (CAR) T Cells Were Detected in the Blood(119 days after CAR T-cell infusion)
- Number of Participants With Clinical Response(Approximately 1 year 5 months)
研究者
James Kochenderfer, M.D.
Principal Investigator
National Cancer Institute (NCI)