A Phase 1 Study of Chimeric Antigen Receptor Modified T-cells Targeting NKG2D-Ligands in Patients With Acute Myeloid Leukemia (AML)/Advanced Myelodysplastic Syndrome (MDS-RAEB) and Multiple Myeloma.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Safety and feasibility of intravenous administration of CM-CS1 T-cells.
研究概览
简要总结
This Phase I clinical trial is evaluating chimeric-antigen receptor (CAR) T-cells (CM-CS1 T cells) which recognize NKG2D-ligands on the surface of cancer cells. This study evaluates the safety and feasibility of administering a single intravenous dose of CM-CS1 CAR T-cells to patients with AML, MDS-RAEB and Multiple Myeloma.
详细描述
This is a study for patients with AML or MDS-RAEB that is not in remission and for which there are no reasonable standard treatment options and for patients with relapsed/refractory multiple myeloma with progressive disease.
In this study, the participant's white blood cells (T-cells) will be collected and modified such that the T-cells are able to recognize specific molecules (called NKG2D-ligands), that are expressed on the surface of cancer cells in these diseases. This modification is a genetic change to the T-cells. The modified T cells, called CM-CS1 T-cells, are then given back to the participant by a single intravenous infusion. In this study, participants will not receive any chemotherapy prior to infusion of the CM-CS1 T-cells.
The study will evaluate whether it is safe and feasible to administer CM-CS1 T-cells to participants with AML/MDS-RAEB and multiple myeloma. It will also evaluate whether the CM-CS1 T-cells have a beneficial effect against the cancer cells. Another goal of the study is to learn more about the persistence and function of the CM-CS1 T-cells in the body.
Participants will be followed very closely during the first month after infusion. They are required to remain within 50 miles of Brigham and Women's Hospital (Boston, MA) for 10 days after the infusion and will be followed three times per week for the first 21 days and at day 28. Subsequently, participants will be followed monthly until 6 months after infusion, every 3 months until 15 months after infusion and at 24 months after infusion. Because this study involves gene transfer, participants will be followed yearly for up to 15 years.
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 —（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
- •Participants who have received chemotherapy or radiotherapy within 3 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier.
- •Concurrent systemic steroid or other immunosuppressive therapy.
- •Participants who are concurrently receiving any other investigational agents, or have received another investigational agent within 3 weeks before enrollment.
- •Participants who have received prior allogeneic stem cell transplantation, gene therapy, or adoptive T-cell therapy.
- •Active infections necessitating use of treatment antibiotics/antivirals during the screening period (prophylaxis is acceptable) or evidence of an active communicable infectious disease.
- •Participants who underwent major surgery within 4 weeks before day 0 of planned CM-CS1 T-cell infusion (this does not include placement of vascular access device or tumor biopsies).
- •Participants with any known history of primary immunodeficiency.
- •History of allergic reactions or hypersensitivity attributed to Human serum albumin or Plasma-lyte A.
- •Uncontrolled intercurrent illness or serious uncontrolled medical disorder
- •Pregnancy or breastfeeding
- •Known HIV-positive participants are ineligible because the effect of transducing HIV-infected lymphocytes with the chimeric NKG2D- transgene on the disease course is unknown.
- •Clinically relevant active infection including active hepatitis B or C or any other concurrent disease which in the judgment of the Investigator would make the subject inappropriate for enrollment on this study.
- •Active autoimmune disease
- •History of a malignancy other than one of the malignancies in this study with exception of the following circumstances:
- •Patients with a history of malignancy who have been adequately treated and have been disease-free for at least 2 years are not excluded.
- •Patients with adequately treated active non-invasive cancers (such as non-melanomatous skin cancer or in-situ bladder, cervical and breast cancers) are not excluded.
- •Unwillingness to use an effective contraceptive method during the study and at least 4 months after administration of CM-CS1 T-cells unless subject is naturally infertile.
研究组 & 干预措施
CM-CS1 T-cell infusion
The treatment will consist of a single infusion of CM-CS1 cells.
The following dose levels will be evaluated:
Cohort 1: 1x 10^6 CM-CS1 T-cells Cohort 2: 3x 10^6 CM-CS1 T-cells Cohort 3: 1x 10^7 CM-CS1 T-cells Cohort 4: 3x 10^7 CM-CS1 T-cells
干预措施: CM-CS1 T-cell infusion (Biological)
结局指标
主要结局
Safety and feasibility of intravenous administration of CM-CS1 T-cells.
时间窗: 24 months
Safety will be defined by the occurence of study-related serious and non-serious adverse events. Feasibility will be defined by the frequency of subjects enrolled who do not receive CM-CS1 T-cells.
次要结局
- Clinical and biologic responses(24 months)