Administration of Tumor-Associated Antigen (TAA)-Specific Cytotoxic T-Lymphocytes to Pediatric Patients With Lymphomas (pediTACTAL)
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Treatment-related adverse event (tAE) Rate
研究概览
简要总结
Investigators have previously used this sort of therapy to treat Hodgkin or non-Hodgkin lymphoma that is associated with the virus that causes infectious mononucleosis ("mono" or the "kissing disease"), Epstein-Barr virus (EBV). EBV is found in cancer cells of up to half of all patients with Hodgkin's and non-Hodgkin lymphoma. This suggests that it may play a role in causing lymphoma. The cancer cells infected by EBV are able to hide from the body's immune system and escape being killed. Investigators previously tested special white blood cells (cells that help the body fight disease and infection), called T cells. The T cells were trained to kill EBV-infected cells and were tested to see whether treatment with these cells could affect these tumors. In many patients investigators found that giving these trained T cells caused a complete or partial response.
However, many patients do not have EBV found in their lymphoma cells. Therefore, investigators now want to test whether special T lymphocytes directed against other types of proteins that show on the tumor cell surface can result in similar promising results. The proteins that will be targeted 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 stage of the study, investigators will target five TAAs which commonly show on lymphoma cells , called NY-ESO-1, MAGEA4, PRAME, Survivin and SSX. Investigators will do this by using special types of T cells called cytotoxic T lymphocytes (CTLs) generated in the lab. These TM-specific T cells are an investigational product not yet approved by the U.S. Food and Drug Administration.
The purpose of this stage of the study is to find out if TM-specific cytotoxic T cells are safe in children. The investigators want to learn what the side-effects are, and to see whether this therapy might help treat patients who are considered high risk for relapse of Hodgkin disease or non-Hodgkin lymphoma.
详细描述
First, patients provide blood for us to make TAA-specific cytotoxic T cells in the lab. The amount of blood to be drawn will be less based on the child's weight per blood draw (3 mL/kg). Under certain conditions related to the patient's health, investigators may need to collect the blood using a process called apheresis. Apheresis is the process where blood is passed through a machine that separates out the components of the patient's blood that is needed. The remainder of the patient's blood is then returned to the patient's body.
If the TAA-specific cytotoxic T cells can be made, the time from collection of the blood to manufacture of T cells for administration to the patient is about 1 to 2 months.
The cells will then be injected by IV into the patient over 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 administration. Initially, two doses of T cells will be given two weeks apart. The patient's lymphoma will be assessed before the infusion (pre-infusion) and then 6 weeks after the second infusion. If after the patient's second infusion he/she has not relapsed or experienced a side effect which would prevent him/her from receiving any more cells, he/she can receive up to six (6) additional doses if they wish. The T cells would then be given at 6-8 week intervals.
In between the first and second T cell infusions and for 6 weeks after the last infusion, investigators ask that the patient not receive any other anti-cancer treatments such as radiation therapy or chemotherapy. 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. All of the treatments will be given by the Center for Cell and Gene Therapy at Texas Children 's Hospital.
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
- 1 Year 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Any pediatric patient (age ≥ 1 year and ≤ 21 years), regardless of sex, with a diagnosis of Hodgkin or non-Hodgkin Lymphoma.
- •Patients with life expectancy > 6 weeks.
- •Hgb ≥ 7.0 (transfusions allowed).
- •Informed Consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. If applicable, patient assents to procurement,
- •Procurement
排除标准
- •Patients with severe intercurrent infection.
- •Patients with active HIV, Hepatitis B, or Hepatitis C infection at time of procurement (can be pending at the time of blood draw).
- •Patients receiving systemic corticosteroids at the time of or within one week prior to procurement.
- •Presence of grade 2-4 acute GVHD or active chronic GVHD > mild global severity score.
- •Treatment Inclusion Criteria:
- •Any pediatric patient (age ≥ 1 year and ≤ 21 years), regardless of sex, with a diagnosis of Hodgkin or non-Hodgkin Lymphoma who are in complete remission (CR), but at high risk for relapse (specifically, who are stage 3 or stage 4 at diagnosis, are in second complete remission (CR2), and who have previously received >2 lines of lymphoma-directed therapy).
- •Pulse oximetry of > 90% on room air in patients who previously received radiation therapy.
- •Patients with a Karnofsky/Lansky score of > 60
- •Patients with bilirubin < 3x upper limit of normal
- •Patients with a creatinine ≤ 2x upper limit of normal for age.
- •Patients with AST < 3x upper limit of normal.
- •Patients with Hgb ≥ 7.0 (transfusions allowed)
- •Acceptable organ function based on clinical or laboratory findings according to investigator discretion
- •Patients should have been off other investigational therapy for one month prior to entry in this study.
- •Patients should have been off conventional therapy including rituximab for at least 1 week prior to entry in this study, and at least 4 weeks since last dose of radiation (if applicable)
- •Informed Consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. If applicable, patient assents to participation in trial.
- •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:
- •Patients with severe intercurrent infection.
- •Presence of grade 2-4 acute GVHD or active chronic GVHD > mild global severity score.
- •Patients receiving systemic corticosteroids > 0.5mg/kg prednisone or equivalent.
- •Pregnant or breastfeeding.
- •Active viral infection with HIV or hepatitis type B or C. "Active" infection defined as infectious disease testing indicating that patient blood is reactive for Hep B, C and/or HIV and confirmed using PCR to measure viral load.
研究组 & 干预措施
Experimental Arm
Patients receiving autologous TAA-specific cytotoxic CTLs
干预措施: TAA-specific CTLs (Biological)
结局指标
主要结局
Treatment-related adverse event (tAE) Rate
时间窗: 8 weeks post first CTL infusion
Treatment-related adverse event (tAE) rate is the proportion of participants with tAE measured by the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The tAE will be defined as development of Grade III-IV events in any organ system that do not return to grade I within 72 hours with the exception of events that are clearly unrelated, and, of hematological toxicities, which are only considered a tAE if Grade III persisting for up to 10 days or greater than or equal to Grade IV. In addition grade 2 or greater autoimmune reaction will be considered a tAE.
次要结局
- Obtain information on the expansion, persistence and anti-tumor effects of the adoptively-transferred TAA-specific CTLs(8 weeks)
研究者
Lauren Scherer
Clinical Instructor
Baylor College of Medicine