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Administration of LMP2a-Specific Cytotoxic T-Lymphocytes Following CD45 Antibody to Patients With Relapsed EBV-Positive Hodgkin's or Non-Hodgkin's Lymphoma

Phase 1
Open (Enrolling)

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Trial Information

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.

Inclusion Criteria:

- Any patient, regardless of age or sex, with EBV-positive Hodgkin's or non-Hodgkin
lymphoma, regardless of the histological subtype or EBV-associated T/NK cell
Lymphoproliferative disease. This includes patients in second or subsequent relapse
including post autologous or syngeneic stem cell transplant (or with active disease
or in first relapse if immunosuppressive chemotherapy contraindicated or if the
patient has relapsed multiple times and is currently in remission but has a high risk
of relapse). (group A) OR Patients who have relapsed after allogeneic stem cell
transplant for Hodgkin's Lymphoma or non-Hodgkin's Lymphoma (Group B)

- Life expectancy of more than 6 weeks

- No severe intercurrent infection

- Patient, parent/guardian able to give informed consent

- Donor must be HIV negative (if autologous product used - patient must be HIV

- Bilirubin less than or equal to 3x normal

- AST less than or equal to 5x normal

- Hgb higher than 8.0 g/L

- Creatinine less than or equal to 2x normal for age

- Patients should have been off other investigational therapy including T cells
therapies for one month prior to entry in this study

- Karnofsky score of over or equal to 50

- No evidence of GVHD >Grade II at time of enrollment

- Female patients with reproductive capacity must have a negative pregnancy test

Exclusion Criteria:

- Patient, parent/guardian unable or unwilling to give informed consent

- Pregnant women

- Patients with a Karnofsky score of < 50

- Patients with a severe intercurrent infection

- Patients with a life expectancy of <6 weeks

- Patients with a bilirubin of more than 3x normal. AST of more than 5x normal

- Patients with a creatinine of more than 2x normal for age

- GVHD greater than Grade II at time of enrollment

- Due to unknown effects of this therapy on a fetus, pregnant women are excluded from
this research. The male partner should use a condom

Note: Patients who would be excluded from the protocol strictly for laboratory
abnormalities can be included at the investigator's discretion after approval by the CCGT
Protocol Review Committee and the FDA reviewer.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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).

Outcome Time Frame:

15 years

Safety Issue:


Principal Investigator

Catherine M Bollard, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Baylor College of Medicine


United States: Food and Drug Administration

Study ID:




Start Date:

October 2003

Completion Date:

April 2012

Related Keywords:

  • Lymphoma
  • Hodgkins
  • Non-Nodgkins
  • Lymphoma
  • Lymphoma
  • Lymphoma, Non-Hodgkin



Baylor College of Medicine Houston, Texas  77030
Texas Children's Hospital Houston, Texas  
The Methodist Hospital Houston, Texas  77030