Administration of LMP2a-Specific Cytotoxic T-Lymphocytes Following CD45 Antibody to Patients With Relapsed EBV-Positive Hodgkin's or Non-Hodgkin's Lymphoma
We first tested a biopsy of the tumor that has already been done to see if the tumor cells
are EBV positive. We then got permission to take up to 60ml (12 teaspoonfuls) of blood from
the patient or their donor on one or two occasions. We used this blood to grow T cells in
the laboratory. We first grew a special type of cell called dendritic cells stimulate the T
cells and we put a specially produced human virus (adenovirus) that carries the LMP-2a gene
into the dendritic cells. These dendritic cells were then treated with radiation so they
could not grow. They were then used to stimulate T cells. This stimulation trained the T
cells to kill cells with LMP-2a on their surface. We then grew these LMP-2a specific CTLs by
more stimulation with EBV infected cells (which we made from the patients blood or their
donor's blood by infecting them with EBV in the laboratory). We also put the adenovirus that
carries the LMP2 gene into these EBV infected cells so that we increase the amount of LMP2
that these cells have. Again, these EBV infected cells were treated with radiation so they
could not grow. Once we made sufficient numbers of T cells we tested them to make sure they
kill cells with LMP2a on their surface. These cells are now ready to give to the patient if
they agree to being on this study.
We also took up to 500 ml (2 1/2 cups) of extra blood from the patient or their donor, which
we froze. In case the patients own cells do not recover as we expect after the antibody and
cell infusions, we can thaw these cells and give them back to the patient.
If the patient agrees to this treatment they will get treated with the CD45 antibodies for 4
days in a row and then 2-3 days later get a dose of LMP2 specific CTLs. If they are a female
of child-bearing potential, we will give the patient a pregnancy test at least one week
prior to the infusion. If they are pregnant, the patient will not be able to participate in
the study. The study doctor will be notified.
The CD45 antibodies will be given to the patient through a vein for 6-8 hours and we will
monitor the patient for at least 6 hours after the infusion. After the infusion we will
check the levels of CD45 in the blood at 24 hours (optional) and/or at 48-72 hours after the
last infusion to check the level is low enough to give the patient the CTLs.
The CTLs will be thawed and injected through a central line, if the patient has one, or
through a vein in their arm over 10 minutes, after pretreatment with Tylenol and Benadryl.
Because the cells are frozen in a preservative called DMSO which is breathed out through the
lungs they will have a funny taste in their mouth for a few minutes after getting the cells
in addition the DMSO may make the patients breath smell like garlic. We will then monitor
them in clinic for 4 hours after the injection.
All of the treatments will be given by the Center for Cell and Gene Therapy at Texas
Children's Hospital or the Methodist Hospital. We will follow the patient in the clinic
after the CTL injection. If there is a reduction in the size of the lymphoma on CT or MRI
scans as assessed by a radiologist, they can receive up to six additional doses of the T
cells if they wish.
To learn more about the way the T cells are working and how long they last in the body, an
extra 10-60 mls (2-12 teaspoonfuls) of blood will be taken on the days of the CD 45 antibody
infusions, before and at the end of the CTL injection, as well as 3-4 days (taking blood on
this day is optional) 1, 2, 4, 6 and 8 weeks after the CTL injections and then at 3,6,9 and
12 months. We will use this blood to look at the immune response in the blood to the
patients cancer. In addition to the blood draws, because the patient has received cells that
have been stimulated with cells that have a new gene the patient will need to be followed
yearly for the next ten years so we can see if there are any long term side effects of the
gene transfer. In the event of death, we will request permission to perform an autopsy to
learn more about the effects of the treatment on the disease.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
2.1 To determine the safety of autologous/syngeneic or allogeneic LMP-2 specific cytotoxic T-lymphocytes (CTL) in combination with CD45 monoclonal antibody (Mab) in patients with EBV positive Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL).
Catherine M Bollard, MD
Baylor College of Medicine
United States: Food and Drug Administration
|Baylor College of Medicine||Houston, Texas 77030|
|Texas Children's Hospital||Houston, Texas|
|The Methodist Hospital||Houston, Texas 77030|