Tumor Associated Antigen (TAA)-Specific Cytotoxic T-Lymphocytes Administered to Patients With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 4
- 主要终点
- Number of patients with dose-limiting toxicity.
研究概览
简要总结
This is a clinical trial for patients with a solid tumor which has come back, or may come back, or has not gone away after treatment, including the standard treatment we know for these diseases. This is a study using special immune system cells called tumor-associated antigen (TAA)-specific cytotoxic T lymphocytes, a new experimental therapy.
The proteins that the investigators are targeting in this study are called tumor-associated antigens (TAAs). These are cell proteins that are specific to the cancer cell, so they either do not show or show up in low quantities on normal human cells. In this study, the investigators target five common TAAs called NY-ESO-1, MAGEA4, PRAME, Survivin and SSX. On a different study, patients have been treated and so far this treatment has shown to be safe.
The investigators now want to try this treatment in patients with solid tumors.
This protocol is designed as a Phase I dose-escalation study.
详细描述
Blood will be collected from the patient and TAA-specific CTLs will be made.
The cells will be injected by IV into the patient over 1 - 10 minutes. The patient may be pre-treated with acetaminophen (Tylenol) and diphenhydramine (Benadryl). Acetaminophen (Tylenol) and diphenhydramine (Benadryl) are given to prevent a possible allergic reaction to the T cell infusion. Initially, two doses of T cells will be given two weeks apart. The patient's disease will be assessed pre-infusion and then 6 weeks after the second infusion. If after the second infusion, there is a reduction in size of the patient's tumor or if the tumor remains stable on CT or MRI scan as assessed by a radiologist, the patient can receive up to six (6) additional doses of the T cells at monthly intervals. All of the treatments will be given by the Center for Cell and Gene Therapy at Houston Methodist Hospital or Texas Children's Hospital.
In between the first and second T cell infusions, and for 6 weeks after the last infusion, the investigators ask that the patient not receive any other anti-cancer treatments, such as radiation therapy or chemotherapy, except PD1/PDL1 inhibitors as clinically indicated. If the patient does receive any other therapies in-between the first and second infusion of T cells, they will be taken off treatment and will not be able to receive the second infusion of T cells.
This is a dose escalation study. This means that at the beginning, patients will be started on the lowest dose (1 of 4 different levels) of T cells. Once that dose schedule proves safe, the next group of patients will be started at a higher dose. This process will continue until all 4 dose levels are studied. If the side effects are too severe, the dose will be lowered or the T cell injections will be stopped.
MEDICAL TESTS BEFORE TREATMENT:
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
- 2 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Any patient regardless of sex with a solid tumor expressing any of the following antigens (PRAME, SSX2, MAGEA4, NY-ESO1-1 and/or Survivin) with:
- •Active disease after first line therapy;
- •Refractory disease;
- •As adjuvant therapy for high risk disease (high risk disease is a disease that has a >50% risk of progression within 5 years)
- •Patients with life expectancy at least 6 weeks.
- •Age greater than or equal to 2 and less than or equal to 80 years old.
- •Informed Consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
- •Procurement
排除标准
- •Diagnosis of primary CNS tumor.
- •Patients with severe intercurrent infection.
- •Patients with active HIV infection at time of procurement (can be pending at the time of blood draw).
- •Patients in remission who are enrolled on another study where time to progression or disease-free survival is a primary endpoint.
- •Treatment Inclusion Criteria:
- •Any patient regardless of sex with a solid tumor expressing any of the following antigens (PRAME, SSX2, MAGEA4, NY-ESO1-1 and/or Survivin) with:
- •Active disease after first line therapy;
- •Refractory disease;
- •As adjuvant therapy for high risk disease (high risk disease is a disease that has a >50% risk of progression within 5 years)
- •Patients with life expectancy at least 6 weeks.
- •Age greater than or equal to 2 and less than or equal to 80 years old.
- •Pulse oximetry of >95% on room air in patients who previously received radiation therapy.
- •Patients with a Karnofsky/Lansky score of greater than or equal to
- •Patients with bilirubin less than or equal to 2x upper limit of normal, AST less than or equal to 3x upper limit of normal, and Hgb >8.0
- •Patients with a creatinine less than or equal to 2x upper limit of normal for age.
- •Patients should have been off other investigational therapy for one month prior to entry in this study.
- •Patients should have been off conventional therapy for at least 1 week prior to entry in this study. PD1/PDL1 inhibitors will be allowed if medically indicated.
- •Informed Consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
- •Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research. The male partner should use a condom Females of child-bearing potential must be willing to utilize one of the more effective birth control methods during the study unless female has had a hysterectomy or tubal ligation.
- •Treatment Exclusion Criteria:
- •Diagnosis of primary CNS tumor.
- •Patients with severe intercurrent infection.
- •Patients receiving systemic corticosteroids (patients off steroids for at least 48 hours are eligible).
- •Pregnant or breastfeeding
- •HIV positive.
- •Patients in remission who are enrolled on another study where time to progression or disease-free survival is a primary endpoint.
结局指标
主要结局
Number of patients with dose-limiting toxicity.
时间窗: 8 weeks
The Phase I dose escalation trial is designed for the primary goal of evaluating the safety and feasibility of administering TAA-CTLs to patients with solid tumors.
次要结局
- Number of patients with a disease response to the CTLs.(8 weeks)
研究者
Sarah Whittle
Assistant Professor, Pediatric Hematology/Oncology, Center for Cell and Gene Therapy
Baylor College of Medicine