Epstein Barr Virus (EBV) Specific Cytotoxic T-Cells, Relapsed Lymphoma, ANGEL
- Conditions
- Epstein-Barr Virus-Related Hodgkin LymphomaEBV Positive Plasma Cell NeoplasmEpstein-Barr Virus-Related Non-Hodgkin Lymphoma
- Interventions
- Biological: Injection of EBV Specific CTLs
- Registration Number
- NCT00058617
- Lead Sponsor
- Baylor College of Medicine
- Brief Summary
Patients have a type of lymph gland cancer called Hodgkin or non-Hodgkin Lymphoma which has come back or not gone away after treatment, including the best treatment known for relapsed Lymphoma.
Patients are being asked to volunteer to be in a research study using Epstein Barr virus specific cytotoxic T lymphocytes, a new experimental therapy. This therapy has never been used in patients with Hodgkin disease or this type of non-Hodgkin Lymphoma but it has been used successfully in children with other types of blood cancer caused by EBV after bone marrow transplantation. Some patients with Hodgkin or non-Hodgkin Lymphoma show evidence of infection with the virus that causes infectious mononucleosis Epstein Barr virus before or at the time of their diagnosis of the Lymphoma. EBV is often found in the cancer cells suggesting that it may play a role in causing Lymphoma. The cancer cells infected by EBV are very clever because they are able to hide from the body's immune system and escape destruction. Investigators want to see if it's possible to grow special white blood cells, called T cells, that have been trained to kill EBV infected cells.
Purpose The purpose of this study is to find the largest safe dose of EBV specific cytotoxic T cells, to learn what the side effects are and to see whether this therapy might help patients with Hodgkin disease and non-Hodgkin Lymphoma.
- Detailed Description
The investigators will take 60-70 ml (12 teaspoonfuls) of blood from the patient to make a B cell line called a lymphoblastoid cell line or LCL by infecting the blood with a laboratory strain of EBV called B95-8. The investigators will then use this EBV infected cell line (which have been treated with radiation so that they cannot grow) as stimulator cells and mix it with more blood. This stimulation will train the T cells to kill EBV infected cells and result in the growth of an EBV specific T cell line. The investigators will then test the T cells to make sure that they kill the EBV infected cells and not normal cells and freeze them.
Patients will be entered into one of three different dosing schedules being evaluated. Three to six patients will be evaluated on each dosing schedule. Escalation will continue until irreversible or life threatening side effects considered to be related to the T cells are seen.
The cells will then be thawed and injected into the patients' vein over 10 minutes, after pretreatment with Tylenol and Benadryl. Tylenol and 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. If after the second infusion there is a reduction in the size of the patient's lymphoma on CT or MRI scan as assessed by a radiologist, the patient can receive up to six additional doses of the T cells. All of the treatments will be given at Texas Children's Hospital or the Methodist Hospital.
Patients will be followed in the clinic after the injections. To learn more about the way the T cells are working and how long they last in the body, an extra 40 mls (8 teaspoonfuls) of blood will be taken before each infusion and then 24 hours after each infusion, 3-4 days after each infusion and at 1, 2, 4, and 6 weeks post infusion and then at 3, 6, 9 and 12 months post infusion. The blood may be drawn from the central line at the time of regular blood tests. This blood will be used to test for the frequency and activity of EBV specific T cells. A total of at least 122 teaspoons (approximately 40 tablespoons) of blood will be collected during participation in this study.
If the patient decide to withdraw at any time during the study both samples and data collected during participation will be maintained.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 13
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Injection of EBV Specific CTLs Injection of EBV Specific CTLs Subjects will receive autologous EBV Specific CTLs. Patients that agree will recieve CTLs that have been marked with the neomycin resistance gene.
- Primary Outcome Measures
Name Time Method The safety of two IV injections of auto EBV specific CTLs will be determined through adverse event measurement. These CTLs may be marked with the neomycin resistance gene introduced by a retroviral vector. 6 weeks Three patients will be enrolled at the first dose level and followed for six weeks after the second dose (which will constitute a course) for evaluation of any critical toxicity. The toxicity will be evaluated as per the NCI Common Toxicity criteria version 2.0.Any toxicity scored as Grade 3 or 4 according to this criteria will be classified as an adverse event. If no toxicity is observed in the first three patients then we will enroll another three patients at the next dose level. However, if toxicity is observed in no more than one out of the three patients then three more patients will be enrolled at the same dose level. Now if the toxicity is observed in no more than one out of the six patients then we will advance to the next dose level and enroll three new patients. If toxicity is observed in two or more patients out of six then the dose limiting toxicity (DLT) has been exceeded and the previous dose level will be considered as the maximum tolerated dose (MTD) level.
To determine the feasibility of generating EBV specific cytotoxic T cell lines from patients with active EBV positive Lymphoma including Hodgkin Disease (HD) or Non-Hodgkin Lymphoma (NHL). 6 weeks To determine the survival, immunological efficacy and anti-tumor effects of EBV specific cytotoxic T-lymphocyte lines. 15 years During the course of the study the survival, immunological efficacy and anti-tumor activity of neomycin resistance gene marked EBV specific cytotoxic T-lymphocyte lines will also be studied. In order to gain reasonable insight into the anti-tumor activity and late toxicity the patients will be followed for a total of twelve weeks.In the present case, the chances of observing any late toxicity should be if anything lower, as in this case the CTLs will be derived autologously.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (2)
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States