LMP-specific T-cells for Patients With Relapsed EBV-positive Lymphoma
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Cancer, Lymphoma |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 5/20/2016 |
| Start Date: | April 2007 |
| End Date: | April 2018 |
Administration of LMP-Specific Cytotoxic T-Lymphocytes to Patients With Relapsed EBV-Positive Lymphoma (ALCI)
Patients have a type of lymph gland disease (HD or NHL, Lymphoepithelioma, 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 known for these diseases. This research
study uses 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 NHL, 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. Investigators 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.
The Investigators 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. The
investigators grew T cells in the lab that recognized all 9 proteins and were able to
successfully prevent and treat post transplant lymphoma. However, in HD and NHL and SCAEBV,
the tumor cells and B cells only express 2 EBV proteins. In a previous study, T cells were
made that recognized all 9 proteins and were given to patients with HD. Some patients had a
partial response to this therapy but no patients had a complete response. The investigators
think one reason may be that many of the T cells reacted with proteins that were not on the
tumor cells. In this study, they are trying to find out if they 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 FDA.
The purpose of this study is to find the largest safe dose of LMP-specific cytotoxic T
cells, to learn what the side effects are and to see whether this therapy might help
patients with HD, NHL, Lymphoepithelioma, SCAEBV or leiomyosarcoma.
active EBV (SCAEBV), or leiomyosarcoma) which has come back or may come back or has not gone
away after treatment, including the best treatment known for these diseases. This research
study uses 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 NHL, 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. Investigators 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.
The Investigators 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. The
investigators grew T cells in the lab that recognized all 9 proteins and were able to
successfully prevent and treat post transplant lymphoma. However, in HD and NHL and SCAEBV,
the tumor cells and B cells only express 2 EBV proteins. In a previous study, T cells were
made that recognized all 9 proteins and were given to patients with HD. Some patients had a
partial response to this therapy but no patients had a complete response. The investigators
think one reason may be that many of the T cells reacted with proteins that were not on the
tumor cells. In this study, they are trying to find out if they 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 FDA.
The purpose of this study is to find the largest safe dose of LMP-specific cytotoxic T
cells, to learn what the side effects are and to see whether this therapy might help
patients with HD, NHL, Lymphoepithelioma, SCAEBV or leiomyosarcoma.
Investigators 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,
investigators will then take 60 mL (about 12 teaspoons) of blood from the patient or their
donor on one or two occasions. They will use this blood to grow T cells. First they will
grow a special type of cells called dendritic cells or monocytes which will stimulate the T
cells. Next they will put a specially produced human virus 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. Investigators
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 sufficient numbers of T cells have been made, investigators will test them to make sure
they kill cells with LMP on their surface. If the counts are low they may need to obtain
additional blood samples to make these cells. Prior to giving the patient the CTLs, the
cells will be tested to make sure they don't attack the tissue.
The cells will then be thawed and injected into the patient over 10 minutes. 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.
For follow-up after the CTL infusions, the patient will be seen every 3 months for the first
year. Then the patient will either be seen in the clinic or they will be contacted by a
research nurse yearly for 5 years.
to see if the tumor or tissue cells are EBV positive. If the patient is eligible,
investigators will then take 60 mL (about 12 teaspoons) of blood from the patient or their
donor on one or two occasions. They will use this blood to grow T cells. First they will
grow a special type of cells called dendritic cells or monocytes which will stimulate the T
cells. Next they will put a specially produced human virus 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. Investigators
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 sufficient numbers of T cells have been made, investigators will test them to make sure
they kill cells with LMP on their surface. If the counts are low they may need to obtain
additional blood samples to make these cells. Prior to giving the patient the CTLs, the
cells will be tested to make sure they don't attack the tissue.
The cells will then be thawed and injected into the patient over 10 minutes. 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.
For follow-up after the CTL infusions, the patient will be seen every 3 months for the first
year. Then the patient will either be seen in the clinic or they will be contacted by a
research nurse yearly for 5 years.
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#
(#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)
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 or subsequent 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.
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.
We found this trial at
2
sites
Texas Children's Hospital Texas Children's Hospital, located in Houston, Texas, is a not-for-profit organization whose...
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