GPC-3 Chimeric Antigen Receptor T Cells FOR Recurrent GPC-3 Positive Glioblastoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Number of Patients with Dose Limiting Toxicity
研究概览
简要总结
The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells.
Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T-cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat participants with cancers. They have shown promise, but have not been strong enough to cure most participants.
The study team has found from previous research that we can put a new gene (a tiny part of what makes-up DNA and carries the participants traits) into T cells that will make them recognize cancer cells and kill them. In the lab, the study team has made several genes called a chimeric antigen receptor (CAR), from an antibody called GC33. The antibody GC33 recognizes a protein found on the participants brain tumor. This CAR is called GPC3-CAR. To make this CAR more effective, the study has also added a gene that includes IL15. IL15 is a protein that helps CAR T cells grow better and stay in the blood longer so that they may kill tumors better. The mixture of GPC3-CAR and IL15 killed tumor cells better in the laboratory when compared with CAR T cells that did not have IL15. This study will test T cells with the IL15 GPC3-CAR (GO-CART T cells) in participants with GPC3-positive brain tumors.
T cells made to carry a gene called iCasp9 can be killed when they encounter a specific drug called AP1903. The study team will insert the iCasp9 and IL15 together into the T cells using a virus that has been made for this study. The drug (AP1903) is an experimental drug that has been tested in humans with no bad side-effects. The study team will use this drug to kill the T cells if necessary due to side effects.
This study will test T cells genetically engineered with a GPC3-CAR and IL15 (GO-CART T cells) in participants with GPC3-positive brain tumors.
The GO-CART T cells are an investigational product not approved by the Food and Drug Administration.
详细描述
The study team will collect up to 180 mL (approximately 12 tablespoons) of participants blood. This will be used to grow T cells. The study team grows the T cells and uses a retrovirus (a special virus that can insert the GPC3 CAR and IL15 genes into the T cells) to genetically engineer them. After the CAR and IL15 genes were put into the T cells, the study team ensures that they could kill GPC3 positive solid tumor cells in the laboratory.
WHAT THE TREATMENT WILL BE LIKE:
After making these cells, they were frozen. If the participant agrees to participate in this study, at the time they are scheduled to be treated, the cells will then be thawed and administered in the participants tumor area, called an intracavitary administration, during the participants already scheduled surgical resection. The participant will only get one dose of GO-CART T cells. The participant may be pretreated with Tylenol (acetaminophen) and Benadryl (diphenhydramine). Tylenol and Benadryl are given to prevent a possible allergic reaction to the T cell administration.
In addition to the GO-CART T cell treatment, during surgery the surgeon will place a small device called an Ommaya reservoir. This device consists of a small tube approximately 3 millimeters in diameter whose tip will sit in the normal fluid filled spaces in the participants brain (called the ventricles). The other end of the tube will be attached to a small reservoir that will sit underneath the participants scalp. Ommaya reservoirs are commonly placed in cancer participants to treat participants with cancer cells in the cerebrospinal fluid and pose a low risk of complications. The purpose of this reservoir is to help reduce the pressure in the participants brain should they experience this from the treatment which is an unlikely but reported side effect . The reservoir will also be used to monitor the participants response to the study treatment rather than to administer treatment.
This is a dose escalation study, which means that the study team does not know the highest dose of GO-CART T cells that is safe. To find out, the cells will be given to at least 3 participants at a lower dose. If that is safe, the study team will raise the dose level that is given to the next group of participants. The dose a participant received will get will depend on how many participants get the agent before the participant and how they react. The investigator will tell the participant this information. Since the treatment is experimental, what is likely to happen at any dose is not known.
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
- 21 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Procurement Inclusion Criteria:
- •Diagnosis of GPC3-positive recurrent glioblastoma with previous resection planned for repeat resection.
- •Age ≥18 years
- •Karnofsky score ≥60%
- •Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent
- •GPC3 expression (as determined by immunohistochemistry) with an extent score of ≥ Grade 2 (>25% positive tumor cells) and an intensity score of ≥ 2 (scale 0-4).
- •Procurement
排除标准
- •History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies).
- •History of organ transplantation
- •Known HIV positivity
- •Active bacterial, fungal or viral infection (except Hepatitis B or Hepatitis C virus infections).
- •Exhibits other risk factors of which administration of investigational agent is deemed not in the patient's best interest, in the opinion of the investigator
- •Treatment Inclusion Criteria:
- •Age ≥ 18 years
- •Diagnosis of recurrent glioblastoma with previous resection
- •Karnofsky score ≥ 60%-
- •Stable neurologic exam for 7 days prior to enrollment
- •Stable or decreasing dose of steroids over past 7 days prior to surgery and administration of therapy (max allowable dose is 0.1mg/kg dexamethasone or equivalent per day)
- •Adequate organ function:
- •Creatinine clearance as estimated by Cockcroft Gault or Schwartz ≥ 60 ml/min
- •total bilirubin < 3 times ULN for age
- •absolute neutrophil count > 500/μl
- •platelet count > 100,000/μl (can be transfused but must be achieved prior to enrollment)
- •Hgb ≥ 7.0 g/dl (can be transfused)
- •Pulse oximetry >90% on room air
- •Recovered from acute toxic effects of all prior chemotherapy and investigational agents before entering this study
- •Sexually active patients must be willing to utilize one of the more effective birth control methods for 3 months after the T-cell infusion.
- •Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
- •Treatment Exclusion Criteria:
- •Pregnancy or lactation
- •Uncontrolled infection
- •Known HIV positivity
- •Active bacterial, fungal or viral infection
- •History of organ transplantation
- •History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies)
研究组 & 干预措施
15.GPC3-CAR T cells
GPC3-CAR and IL15 will be administered to patients with GPC3-positive glioblastoma.
干预措施: 15.GPC3-CAR T cells (Genetic)
结局指标
主要结局
Number of Patients with Dose Limiting Toxicity
时间窗: 4 weeks
A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the 15.GPC3-CAR T cells. Specifically those which are Grade 5; hematologic dose-limiting toxicity is any Grade 4 non-hematologic toxicity that fails to return to Grade 2 within 72 hours; Grade 4 allergic reaction to CAR T cell administration; Grade 4 \\reactions due to CRS and neurotoxicity are rarely seen with the use of CAR-based immunotherapy. Grade 3 cytokine release syndrome (CRS) infusion reactions and neurologic toxicity will only be reported to the FDA if they fail to return to Grade 1 within 72 hours. Grade 4 CRS and neurologic toxicities will be reported to the FDA in an expedited fashion.
次要结局
- Response Rate(4 weeks)
- Maximum Tolerated Dose (MTD)(4 weeks)
研究者
Ganesh Rao, MD
Professor
Baylor College of Medicine