View Clinical Trial (Medical Research Study)
Administration of LMP-Specific Cytotoxic T-Lymphocytes to Patients With Relapsed EBV-Positive Lymphoma (ALCI)
| City: |
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Houston |
| State: |
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Texas |
| Zip Code: |
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77030 |
| Conditions: |
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Hodgkin Disease - Non Hodgkin Lymphoma |
| Purpose: |
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Patients have a type of lymph gland disease called Hodgkin or non-Hodgkin Lymphoma or
Lymphoepithelioma or severe chronic active EBV (SCAEBV) or leiomyosarcoma which has come
back or may come back or has not gone away after treatment, including the best treatment we
know for these diseases. We are asking patients to volunteer to be in a research study using
special immune system cells called LMP- specific cytotoxic T lymphocytes, a new experimental
therapy.
Some patients with Lymphoma or SCAEBV or leiomyosarcoma show evidence of infection with the
virus that causes infectious mononucleosis Epstein Barr virus (EBV) before or at the time of
their diagnosis. EBV is found in the cancer cells of up to half the patients with Hodgkin's
and non-Hodgkin Lymphoma, suggesting that it may play a role in causing Lymphoma. The cancer
cells (in lymphoma) and some B cells (in SCAEBV) infected by EBV are able to hide from the
body's immune system and escape destruction. We want to see if special white blood cells,
called T cells, that have been trained to kill EBV infected cells can survive in the blood
and affect the tumor.
We have used this sort of therapy to treat a different type of cancer that occurs after bone
marrow or solid organ transplant called post transplant lymphoma. In this type of cancer the
tumor cells have 9 proteins made by EBV on their surface. We grew T cells in the laboratory
that recognized all 9 proteins and were able to successfully prevent and treat post
transplant lymphoma. However in Hodgkin disease and non-Hodgkin Lymphoma and SCAEBV, the
tumor cells and B cells only express 2 EBV proteins. In a previous study we made T cells
that recognized all 9 proteins and gave them to patients with Hodgkin disease. Some patients
had a partial response to this therapy but no patients had a complete response. We think one
reason may be that many of the T cells reacted with proteins that were not on the tumor
cells. In this present study we are trying to find out if we can improve this treatment by
growing T cells that recognize proteins expressed on EBV infected Lymphoma cells and B cells
called LMP-1 and LMP2. These special T cells are called LMP-specific cytotoxic T-lymphocytes
(CTLs). These LMP-specific cytotoxic T cells are an investigational product not approved by
the Food and Drug Administration.
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| Study Summary: |
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We will first test a biopsy of the tumor or lymph node that has already been done to see if
the tumor or tissue cells are EBV positive. If the patient is eligible, we will then take 60
of blood from the patient or their donor on one or two occasions. We will use this blood to
grow T cells. We will first grow special type of cells called dendritic cells or monocytes
which will stimulate the T cells and we will put a specially produced human viruses that
carries the LMP genes into the dendritic cells or monocytes. They will then be used to
stimulate T cells. This stimulation will train the T cells to kill cells with LMP on their
surface. We will then grow these LMP specific CTLs by more stimulation with EBV infected
cells. These EBV infected cells will be treated with radiation so they cannot grow.
Once we have made sufficient numbers of T cells we will test them to make sure they kill
cells with LMP on their surface. If the counts are low we may need to obtain additional
blood samples to make these cells.
Prior to giving the patient the CTLs we will test the cells to make sure they don't attack
the tissue.
The cells will then be thawed and injected into the patient 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
lymphoma on CT or MRI scan as assessed by a radiologist, the patient can receive up to six
additional doses of the T cells if the patient wishes. This is a dose escalation study which
means that for some patients the second dose may be larger than the first. 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 after the injections. The patient will either be seen in the
clinic or they will be contacted by a research nurse yearly for 5 years. To learn more about
the way the T cells are working in the body, an extra 20-40 mls of blood will be taken
before each infusion and then 4 hours after each infusion(optional), 3-4 days after each
infusion (optional) and then weekly for 2 weeks after each infusion (total of 9 times). Two
weeks after the last infusion, blood will then be taken again and then every 3 months for 1
year, then once a year for 5 years. We will use this blood to see how long the T cells last
and to look at the immune response to the cancer.
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| Criteria: |
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INCLUSION CRITERIA:
1. Any patient, regardless of age or sex, with EBV-positive Hodgkin's or non-Hodgkin's
Lymphoma, or lymphoepithelioma or leiomyosarcoma regardless of the histological
subtype or EBV (associated)-T/NK-lymphoproliferative disease or Severe Chronic EBV*
a - In second or subsequent relapse (or first relapse or with active disease if
immunosuppressive chemotherapy contraindicated or multiply relapsed patients
currently in remission who have a high risk of relapse) OR with primary disease or in
first remission if immunosuppressive chemotherapy is contraindicated, e.g. patients
who develop Hodgkin disease after solid organ transplantation or if the Lymphoma is a
second malignancy e.g. a Richters transformation of CLL.(Group A)
OR
b - In remission or with minimal residual disease status after autologous or
syngeneic SCT for Hodgkin's or non-Hodgkin's Lymphoma/Lymphoepithelioma/SCAEBV.
(Group B)
OR
c - Patients after allogeneic SCT for Hodgkin's Lymphoma or Non-Hodgkin's
Lymphoma/Lymphoepithelioma/SCAEBV. (Group C)
2. Patients with life expectancy 6 weeks or greater.
3. Tumor tissue EBV positive
4. Patients with a Karnofsky/Lansky score of 50 or greater
5. Donor HIV negative (if autologous product - patient must be HIV negative)
6. If post allogeneic SCT must not have less than 50% donor chimerism in either
peripheral blood or bone marrow
7. Patients with bilirubin 3x normal or less, AST 5x normal or less, and Hgb greater
than 8.0
8. Patients with a creatinine 2x normal or less for age
9. Patients should have been off other investigational therapy for one month prior to
entry in this study.
10. Patient, parent/guardian able to give informed consent.
- SCAEBV is defined as patients with high EBV viral load in plasma or PBMC (>4000
genomes per ug PBMC DNA) and/or biopsy tissue positive for EBV
EXCLUSION CRITERIA:
1. Patients with a severe intercurrent infection.
2. Donors who are HIV positive or Patients who are HIV positive if autologous product to
be used
3. Patients with greater than Grade II GVHD
4. 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. Any desired variance from the entry criteria will be discussed
with the IRB and reported annually to the FDA.
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| NCT ID: |
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NCT00062868 |
| Primary Contact: |
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Principal Investigator
Catherine Bollard, MD
Center for Cell and Gene Therapy, Baylor College of Medicine
Catherine M Bollard, MD
Phone: 832-824-4781
Email: cmbollar@txch.org
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| Backup Contact: |
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Email: vxtorran@txch.org
Vicky Torrano
Phone: 832-824-7821
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| Location Contact: |
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Houston, Texas 77030
United States
Catherine M Bollard, MD
Phone: 832-824-4781
Email: cmbollar@txch.org
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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June 19, 2013 |
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