A Phase 1 Study Evaluating the Safety and Activity of Allogeneic CD30 Chimeric Antigen Receptor Epstein-Barr Virus-Specific T Lymphocytes (CD30.CAR-EBVSTs) in Patients With Relapsed or Refractory CD30-Positive Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 4
- 主要终点
- Dose limiting toxicity rate (DLT) by CTCAE 5.0
研究概览
简要总结
This study involved patients that have a cancer called diffuse large B cell lymphoma (DLBCL), NK and T cell lymphomas (NK/TL) or classical Hodgkin lymphoma (cHL) (hereafter these 3 diseases will be referred to as lymphoma). Patients lymphoma has come back or not gone away after treatment. Because there is no standard treatment for the patients cancer at this time or because the currently used treatments do not work fully in all cases, the patients are being asked to volunteer in this research study.
In this study the investigators want to test a type of T cell made from a normal donor. The T cells the investigators will use are called Epstein Barr virus (EBV) specific T cells (EBVSTs) and are cells that the investigators have trained in the laboratory to recognize a EBV which is the virus that causes mono or kissing disease. Some patients with lymphoma have EBV in their cancer cells. Researchers have given T cell lines from normal donor EBVSTs to lymphoma patients who have EBV in their lymphoma cells and have seen responses in about half the patients. The cells have have been generated and are frozen in a bank. The cells are called "allogeneic" (meaning the donor is not related to the patient). CD30.CAR in EBV-specific T cells (called allogeneic CD30.CAR-EBVST) from the blood of healthy donors. The investigators are giving the cells to patients with lymphoma cells that express CD30. If the lymphoma cells also express EBV there may be some benefit from targeting both proteins.
The purpose of this study is to find out the highest safe dose of allogeneic CD30.CAR-EBVST cells given following chemotherapy and used to treat lymphoma. The investigators will learn the side effects of CD30.CAR-EBVST cells in patients and see whether this therapy may help lymphoma patients.
详细描述
Earlier, healthy donors gave blood for us to make CD30.CAR-EBVST cells in the laboratory. These cells were grown and frozen and the investigators will select the donor which the investigators think is the best match for the patient. This is a dose escalation study. This means that at the beginning, patients will be started on the lowest dose (1 of 3 different levels) of CD30.CAR-EBVST cells. Once the lower dose schedule proves safe, the next group of patients will be started at a higher dose. This process will continue until all 3 dose levels are studied. If the side effects are too severe, the dose will be lowered or the T cell infusion will be stopped. Both the risks and benefits of this study may be dose related. The investigators don't know the best dose that will provide benefit while minimizing the risks.
To enroll on this study, patients will need to have recovered from toxic effects of previous chemotherapy and not be receiving any other investigational agents. Patients cannot have received any tumor vaccines within the previous six weeks.
If patients agree to take part in this study, the investigators will ask the patients to adhere to the following study visits and procedure. After patients have signed the consent form, patients are required to come to the hospital for a series of standard medical screening tests, lymphodepletion chemotherapy with cyclophosphamide and fludarabine, infusion with CD30.CAR-EBVST cell treatment and follow-up visits (See details below).
- Screening tests
Screening tests include:
- Blood tests [Human Leukocyte Antigen (HLA) testing] to help us identify the best match for the patient from the banked CD30.CAR-EBVST cells.
- Blood tests for viruses such as human immunodeficiency virus [HIV], human T cell lymphotropic virus [HTLV], hepatitis B virus and hepatitis C virus.
- Tumor biopsy test to check the status of CD30.
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
- 12 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis and clinical course falling into one of the following categories:
- •Hodgkin lymphoma
- •Aggressive non-Hodgkin lymphoma
- •ALK-negative anaplastic T cell lymphoma or other peripheral T-cell lymphoma
- •ALK-positive anaplastic T cell lymphoma
- •CD30-positive tumor as assayed in a CLIA certified Pathology Laboratory.
- •Bilirubin 2 times (or 3 times if the patient has Gilbert syndrome) or less than the upper limit of normal.
- •AST 3 times or less than the upper limit of normal.
- •Estimated GFR > 70 mL/min.
- •Pulse oximetry of > 90% on room air
- •EKG shows no significant arrhythmias
- •Karnofsky or Lansky score of > 60%.
- •Available allogeneic T cells with ≥15% expression of CD30CAR determined by flow-cytometry.
- •Recovered from all acute non-hematologic toxic effects of all prior chemotherapy.
- •Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom.
- •Informed consent explained to, understood by and signed by patient or guardian. Patient or guardian given a copy of the informed consent form.
排除标准
- •Currently receiving any investigational agents or received any tumor vaccines within the previous six weeks.
- •Received CD30 antibody-based therapy within the previous 4 weeks.
- •History of hypersensitivity reactions to murine protein-containing products.
- •Pregnant or lactating.
- •Tumor in a location where enlargement could cause airway obstruction.
- •Current use of systemic corticosteroids at a dose equivalent to higher than 10 mg/day of prednisone.
- •Active significant, uncontrolled bacterial, viral or fungal infection.
- •Symptomatic cardiac disease (NYHA Class III or IV disease).
结局指标
主要结局
Dose limiting toxicity rate (DLT) by CTCAE 5.0
时间窗: 28 Days
Any Grade 5 event, / Non-hematologic dose-limiting toxicity is any Grade 3 or Grade 4 non-hematologic toxicity that fails to return to Grade 2 within 72 hours, / Grade 2-4 allergic reaction to T-Cells, / Grade 3-4 GVHD, / Grade 3-4 CRS. Toxicity will be evaluated according to the CTCAE Version 5.0. GVHD will be graded by the method of Przepiorka et al.
次要结局
- Rate of Anti-Tumor effect Objective Response (OR)(4 to 12 weeks post CTL infusion)
- Duration of Response(Up to 5 years)
- Stable disease (SD) rate(4 to 12 weeks post CTL infusion)
- Duration of SD(Up to 5 years)
- Progression free survival (PFS)(Up to 5 years)
研究者
Premal Lulla
Assistant Professor
Baylor College of Medicine