A Phase I Clinical Trial of T-cells Expressing an Anti-SLAMF7 CAR for Treating Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Number of Participants That Had Any Grade ≤2, and 3, 4 and 5 Adverse Events Following Administration of T Cells Expressing Anti- Signaling Lymphocytic Activation Molecule F7 (SLAMF7) Chimeric Antigen Receptor (CAR)
研究概览
简要总结
Background:
Multiple myeloma is a blood cancer that is usually incurable. T cells are part of the immune system. Researchers think changing a person's T cells to recognize their cancer could help the person's body kill tumor cells. This is a new approach that uses a patient's own cells to target multiple myeloma.
Objective:
To see if giving anti-Signaling lymphocytic activation molecule F7 (SLAM7) chimeric antigen receptor (CAR) T cells with a stop switch to people with multiple myeloma is safe and to see if adding a gene to stop T-cell activity can limit toxicity of this therapy.
Eligibility:
People ages 18-73 with multiple myeloma for which prior standard treatment has not worked
Design:
Participants will be screened with:
- Medical history
- Physical exam
- Blood, urine, and heart tests
- Bone marrow samples: A needle inserted into the participant's bone will remove marrow.
- Imaging scans: Participants will lie in a machine that takes pictures of the body.
Participants will have apheresis. They will receive a catheter or central line: A plastic tube will be inserted into a chest or arm vein. Blood will be removed and the T cells separated. The rest of the blood will be returned to the participant. The T cells will be manipulated in the lab.
Participants will get chemotherapy through the central line for 3 days.
Participants will receive the manipulated T cells through the central line. They will stay in the hospital at least 9 days.
Participants will have follow-up visits 2 weeks then 1, 2, 3, 4, 6, 9, and 12 months after the infusion. They will then have visits every 6 months for 3 years. Then they will be contacted once per year for 15 years. All visits will include blood tests, and 3 visits will include bone marrow biopsies....
详细描述
Background:
- Multiple myeloma (MM) is a nearly always incurable malignancy of plasma cells.
- T cells can be genetically modified to express chimeric antigen receptors (CARs) that target malignancy-associated antigens.
- Signaling lymphocytic activation molecule F7 (SLAM7) is highly and uniformly expressed on MM cells but is absent on normal tissues except for some leukocytes, including a subset of cluster of differentiation 8 (CD8)+ T cells, natural killer (NK) cells, B cells, plasma cells and monocytes.
- We have constructed a novel anti-SLAMF7 CAR that can specifically recognize SLAMF7- expressing target cells and eradicate SLAMF7-expressing tumors in mice.
- This protocol will test genetic modification of autologous T cells with genes encoding an inducible caspase 9 (IC9) cell-suicide system plus the anti-SLAMF7 CAR.
- Administration of the dimerizer drug Rimiducid (AP1903) is necessary to activate the inducible caspase 9 (IC9) suicide gene and eliminate CAR T cells.
- In this protocol, the suicide gene system will be used to eliminate CAR-expressing T cells in case of severe toxicities caused by the CAR T cells.
- Possible toxicities include cytokine-associated toxicities such as hypotension, and neurological toxicities. Elimination of NK cells and normal plasma cells could make patients more susceptible to infections. Unknown toxicities are also possible.
Objectives:
Primary
- Determine the safety, feasibility of administering T cells expressing an anti-SLAMF7 CAR plus IC9 cell-suicide system to patients with MM.
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
1/Conditioning Chemotherapy Plus Chimeric Antigen Receptor (CAR) T-cells Dose Escalation
Patients will receive escalating doses (up to 4 planned) of Anti-Signaling lymphocytic activation molecule F7 (SLAMF7)-CAR+ T cells infused on day 0 + Cyclophosphamide: 300 mg/m^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 + Fludarabine: 30 mg/m^22 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
干预措施: Cyclophosphamide (Drug)
1/Conditioning Chemotherapy Plus Chimeric Antigen Receptor (CAR) T-cells Dose Escalation
Patients will receive escalating doses (up to 4 planned) of Anti-Signaling lymphocytic activation molecule F7 (SLAMF7)-CAR+ T cells infused on day 0 + Cyclophosphamide: 300 mg/m^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 + Fludarabine: 30 mg/m^22 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
干预措施: Fludarabine (Drug)
1/Conditioning Chemotherapy Plus Chimeric Antigen Receptor (CAR) T-cells Dose Escalation
Patients will receive escalating doses (up to 4 planned) of Anti-Signaling lymphocytic activation molecule F7 (SLAMF7)-CAR+ T cells infused on day 0 + Cyclophosphamide: 300 mg/m^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 + Fludarabine: 30 mg/m^22 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
干预措施: Rimiducid (Drug)
1/Conditioning Chemotherapy Plus Chimeric Antigen Receptor (CAR) T-cells Dose Escalation
Patients will receive escalating doses (up to 4 planned) of Anti-Signaling lymphocytic activation molecule F7 (SLAMF7)-CAR+ T cells infused on day 0 + Cyclophosphamide: 300 mg/m^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 + Fludarabine: 30 mg/m^22 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
干预措施: Anti-Signaling lymphocytic activation molecule F7 (SLAMF7) chimeric antigen receptor (CAR) T cells (Biological)
2/Conditioning Chemotherapy Plus Chimeric Antigen Receptor (CAR) T-cells Expansion Phase
Maximum tolerated dose (MTD) dose of Anti-Anti-Signaling lymphocytic activation molecule F7 (SLAMF7)- CAR T Cells + Cyclophosphamide: 300 mg/m^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 + Fludarabine: 30mg/m^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
干预措施: Cyclophosphamide (Drug)
2/Conditioning Chemotherapy Plus Chimeric Antigen Receptor (CAR) T-cells Expansion Phase
Maximum tolerated dose (MTD) dose of Anti-Anti-Signaling lymphocytic activation molecule F7 (SLAMF7)- CAR T Cells + Cyclophosphamide: 300 mg/m^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 + Fludarabine: 30mg/m^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
干预措施: Fludarabine (Drug)
2/Conditioning Chemotherapy Plus Chimeric Antigen Receptor (CAR) T-cells Expansion Phase
Maximum tolerated dose (MTD) dose of Anti-Anti-Signaling lymphocytic activation molecule F7 (SLAMF7)- CAR T Cells + Cyclophosphamide: 300 mg/m^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 + Fludarabine: 30mg/m^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
干预措施: Rimiducid (Drug)
2/Conditioning Chemotherapy Plus Chimeric Antigen Receptor (CAR) T-cells Expansion Phase
Maximum tolerated dose (MTD) dose of Anti-Anti-Signaling lymphocytic activation molecule F7 (SLAMF7)- CAR T Cells + Cyclophosphamide: 300 mg/m^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 + Fludarabine: 30mg/m^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
干预措施: Anti-Signaling lymphocytic activation molecule F7 (SLAMF7) chimeric antigen receptor (CAR) T cells (Biological)
结局指标
主要结局
Number of Participants That Had Any Grade ≤2, and 3, 4 and 5 Adverse Events Following Administration of T Cells Expressing Anti- Signaling Lymphocytic Activation Molecule F7 (SLAMF7) Chimeric Antigen Receptor (CAR)
时间窗: Date treatment consent signed to date off study, approximately 3 months and 27 days for Level 1, 3 months and 18 days for Level 2, 5 months and 23 days for Level 3, and 1 month and 29 days for Level 4.
Adverse Events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening or disabling, and Grade 5 is fatal.
次要结局
未报告次要终点
研究者
James Kochenderfer, M.D.
Principal Investigator
National Cancer Institute (NCI)