Cytotoxic T Cells to Treat Relapsed EBV-positive Lymphoma
| Status: | Recruiting |
|---|---|
| Conditions: | Cancer, Infectious Disease, Lymphoma, Lymphoma |
| Therapuetic Areas: | Immunology / Infectious Diseases, Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 2/17/2019 |
| Start Date: | November 2013 |
| End Date: | November 2020 |
| Contact: | Catherine Bollard, MD |
| Email: | cbollard@cnmc.org |
| Phone: | 202-476-4776 |
ADMINISTRATION OF LMP-SPECIFIC CYTOTOXIC T-LYMPHOCYTES TO PATIENTS WITH RELAPSED EBV-POSITIVE LYMPHOMA
In this study, investigators are trying to see if LMP specific cytotoxic T lymphocytes (CTLs)
will prevent or treat disease called Epstein Barr Virus (EBV) Disorder including either
Hodgkin Lymphoma or non-Hodgkin Lymphoma or Lymphoepithelioma or severe chronic active EBV
infection syndrome (SCAEBV) or Leiomyosarcoma which has come back or has not gone away after
treatment, including the best treatment. Investigators are using special immune system cells
called third party LMP specific cytotoxic T lymphocytes (CTLs), 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. The investigators want to see if special white
blood cells, called T cells, that have been trained to kill EBV infected cells can survive in
patient's blood and affect the tumor or infection.
Investigators 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. They 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 Lymphoma, the tumor cells and B cells only
express 2 EBV proteins. In a previous study they made T cells that recognized all 9 proteins
and gave them to patients with Hodgkin Lymphoma. Some patients had a partial response to this
therapy but no patients had a complete response. They 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 the
investigators are trying to find out if the investigators 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 third party LMP 1/2 -specific
cytotoxic T-lymphocytes (CTLs). These LMP-specific cytotoxic
T cells are an investigational product not approved by the Food and Drug Administration.
will prevent or treat disease called Epstein Barr Virus (EBV) Disorder including either
Hodgkin Lymphoma or non-Hodgkin Lymphoma or Lymphoepithelioma or severe chronic active EBV
infection syndrome (SCAEBV) or Leiomyosarcoma which has come back or has not gone away after
treatment, including the best treatment. Investigators are using special immune system cells
called third party LMP specific cytotoxic T lymphocytes (CTLs), 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. The investigators want to see if special white
blood cells, called T cells, that have been trained to kill EBV infected cells can survive in
patient's blood and affect the tumor or infection.
Investigators 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. They 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 Lymphoma, the tumor cells and B cells only
express 2 EBV proteins. In a previous study they made T cells that recognized all 9 proteins
and gave them to patients with Hodgkin Lymphoma. Some patients had a partial response to this
therapy but no patients had a complete response. They 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 the
investigators are trying to find out if the investigators 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 third party LMP 1/2 -specific
cytotoxic T-lymphocytes (CTLs). These LMP-specific cytotoxic
T cells are an investigational product not approved by the Food and Drug Administration.
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 a diagnosis of EBV positive Hodgkin's or
non-Hodgkin's Lymphoma or EBV (associated)-T/NK-LPD lymphoproliferative disease or
Lymphoepithelioma/leiomyosarcoma regardless of histological subtype or Severe Chronic
EBV and in remission (group A) or with detectable disease (group B) after allogeneic
SCT
2. Patients with life expectancy > 6 weeks.
3. Tumor tissue EBV positive
4. Patients with a Karnofsky/Lansky score of > 50
5. Donor HIV negative
6. must not have less than 50% donor chimerism in either peripheral blood or bone marrow
7. Patients with bilirubin <2x normal, AST <5x normal, and Hgb >8.0
8. Patients with a creatinine <2x normal 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. Donors who are HIV positive
2. Patients with GVHD > Grade II
3. Due to unknown effects of this therapy on a fetus, pregnant women are excluded from
this research.
We found this trial at
1
site
111 Michigan Ave NW
Washington, District of Columbia
Washington, District of Columbia
(202) 476-5000
Phone: 202-476-4776
Childrens National Medical Center As the nation’s children’s hospital, the mission of Children’s National Medical...
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