CMV-specific Cytotoxic T Lymphocytes Expressing CAR Targeting HER2 in Patients With GBM
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Cancer, Brain Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 12/12/2018 |
| Start Date: | October 2010 |
| End Date: | November 2028 |
Administration of HER2 Chimeric Antigen Receptor Expressing CMV-Specific Cytotoxic T Cells Ins Patients With Glioblastoma Multiforme (HERT-GBM)
This study is for patients that have a type of brain cancer called glioblastoma multiforme
(GBM).
The body has different ways of fighting infection and disease. No single way seems perfect
for fighting cancers. This research study combines two different ways of fighting cancer:
antibodies and T cells. Antibodies are types of proteins that protect the body from
infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special
infection-fighting blood cells that can kill other cells, including cells infected with
viruses and tumor cells. Both antibodies and T cells have been used to treat patients with
cancers. They have shown promise, but have not been strong enough to cure most patients.
The antibody used in this study is called anti-HER2 (Human Epidermal Growth Factor Receptor
2). This antibody sticks to GBM cells because of a substance on the outside of these cells
called HER2. Up to 80% of GBMs are positive for HER2. HER2 antibodies have been used to treat
people with HER2-positive cancers. For this study, the HER2 antibody has been changed so that
instead of floating free in the blood it is now attached to T cells. When an antibody is
joined to a T cell in this way it is called a chimeric receptor. These chimeric receptor-T
cells seem to be able to kill tumors like GBM, but they don't last very long and so their
chances of fighting the cancer are limited. Therefore, developing ways to prolong the life of
these T cells should help them fight cancer.
We found that T cells work better if we also attach a protein called CD28 to the HER2
chimeric receptor (HER2-CAR). In this study we placed this HER2-CAR into T cells that were
pre-selected for their ability to recognize Cytomegalovirus (CMV). This virus exists in most
people. These CMV-specific cytotoxic T cells (CMV-T cells) will be more active since they
will react to the virus as well as to tumor cells. These HER2-CD28 CMV-T cells are an
investigational product not approved by the Food and Drug Administration.
The purpose of this study is to find the largest safe dose of HER2-CD28 CMV-T cells, to learn
what the side effects are, and to see whether this therapy might help patients with GBM.
(GBM).
The body has different ways of fighting infection and disease. No single way seems perfect
for fighting cancers. This research study combines two different ways of fighting cancer:
antibodies and T cells. Antibodies are types of proteins that protect the body from
infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special
infection-fighting blood cells that can kill other cells, including cells infected with
viruses and tumor cells. Both antibodies and T cells have been used to treat patients with
cancers. They have shown promise, but have not been strong enough to cure most patients.
The antibody used in this study is called anti-HER2 (Human Epidermal Growth Factor Receptor
2). This antibody sticks to GBM cells because of a substance on the outside of these cells
called HER2. Up to 80% of GBMs are positive for HER2. HER2 antibodies have been used to treat
people with HER2-positive cancers. For this study, the HER2 antibody has been changed so that
instead of floating free in the blood it is now attached to T cells. When an antibody is
joined to a T cell in this way it is called a chimeric receptor. These chimeric receptor-T
cells seem to be able to kill tumors like GBM, but they don't last very long and so their
chances of fighting the cancer are limited. Therefore, developing ways to prolong the life of
these T cells should help them fight cancer.
We found that T cells work better if we also attach a protein called CD28 to the HER2
chimeric receptor (HER2-CAR). In this study we placed this HER2-CAR into T cells that were
pre-selected for their ability to recognize Cytomegalovirus (CMV). This virus exists in most
people. These CMV-specific cytotoxic T cells (CMV-T cells) will be more active since they
will react to the virus as well as to tumor cells. These HER2-CD28 CMV-T cells are an
investigational product not approved by the Food and Drug Administration.
The purpose of this study is to find the largest safe dose of HER2-CD28 CMV-T cells, to learn
what the side effects are, and to see whether this therapy might help patients with GBM.
When the patient enrolls on this study, they will be assigned to a dose of HER2-CAR CMV-T
cells.
The patient will be given a single injection of cells into the vein through an IV line at the
assigned dose. The injection will take between 1 and 10 minutes. The patient will be followed
in the clinic after the injection for 1 to 4 hours. If later the subject seems to be
experiencing a benefit (confirmed by radiological studies, physical exam and/or symptoms),
s/he may be able to receive up to six additional doses of the T cells if they wish. These
additional infusions would be at least 6 to 12 weeks apart and at the same dose level
received the first time.
Medical tests before treatment--
Before being treated, the patient will receive a series of standard medical tests as follows:
Physical exam, Blood tests to measure blood cells, kidney and liver function, Routine heart
function tests (Echocardiogram),Measurements of the tumor by routine imaging studies
Medical tests during and after treatment--
The patient will receive standard medical tests when getting the infusions and after:Physical
exams, Blood tests to measure blood cells, kidney and liver function, Routine heart function
tests (Echocardiogram) at 6 weeks after the infusion, Measurements of the tumor by routine
imaging studies 6 weeks after the infusion
To learn more about the way the HER2-CAR CMV-T cells are working and how long they last in
the body, blood will be taken on the day of the T-cell infusion, before, 1 hour and 4 hours
after the T-cell infusion, 1, 2, 4 and 6 weeks after the T-cell infusion and every 3 months
for 1 year, every 6 months for 4 years, then yearly for a total of 15 years.
cells.
The patient will be given a single injection of cells into the vein through an IV line at the
assigned dose. The injection will take between 1 and 10 minutes. The patient will be followed
in the clinic after the injection for 1 to 4 hours. If later the subject seems to be
experiencing a benefit (confirmed by radiological studies, physical exam and/or symptoms),
s/he may be able to receive up to six additional doses of the T cells if they wish. These
additional infusions would be at least 6 to 12 weeks apart and at the same dose level
received the first time.
Medical tests before treatment--
Before being treated, the patient will receive a series of standard medical tests as follows:
Physical exam, Blood tests to measure blood cells, kidney and liver function, Routine heart
function tests (Echocardiogram),Measurements of the tumor by routine imaging studies
Medical tests during and after treatment--
The patient will receive standard medical tests when getting the infusions and after:Physical
exams, Blood tests to measure blood cells, kidney and liver function, Routine heart function
tests (Echocardiogram) at 6 weeks after the infusion, Measurements of the tumor by routine
imaging studies 6 weeks after the infusion
To learn more about the way the HER2-CAR CMV-T cells are working and how long they last in
the body, blood will be taken on the day of the T-cell infusion, before, 1 hour and 4 hours
after the T-cell infusion, 1, 2, 4 and 6 weeks after the T-cell infusion and every 3 months
for 1 year, every 6 months for 4 years, then yearly for a total of 15 years.
INCLUSION CRITERIA:
- Histopathological verification of glioblastoma multiforme (GBM: WHO grade IV) with
recurrent or progressive disease after front line therapy.
- HER2 positive GBM
- CMV seropositive
- Normal ECHO (Left ventricular ejection fraction (LVEF) has to be with in normal,
institutional limits)
- Life expectancy 6 weeks or greater
- Karnofsky/Lansky score 50 or greater
- Patient or parent/guardian capable of providing informed consent
- Bilirubin 3x or less than normal, AST 5x or less than normal, creatinine 2x normal or
less for age and Hgb 9.0 g/dl or more; WBC greater than 2,000/ul; ANC greater than
1,000/ul; platelets greater than 100,000/ul
- Pulse oximetry 90% or more on room air
- Sexually active patients must be willing to utilize one of the more effective birth
control methods for 6 months after the CTL infusion. The male partner should use a
condom.
- Available autologous HER2.CAR-transduced CMV-specific cytotoxic T lymphocytes with 15%
or greater expression of HER2.CAR determined by flow-cytometry and killing of
HER2-positive targets 20% or more in cytotoxicity assay.
- Recovered from the acute toxic effects of all prior chemotherapy at least 4 weeks
before entering this study. One exception is Temozolomide(TMZ), an alkylation agent
used as a radiosensitizer and adjuvant chemotherapeutic agent for GBM. Due to the
extremely short half life of TMZ, patients will be allowed to continue receiving it up
to two days prior to cell infusion and cannot restart until six weeks after the
infusion.
EXCLUSION CRITERIA:
- Severe intercurrent infection
- Known HIV positivity
- Pregnant or lactating
- History of hypersensitivity reactions to murine protein-containing products
We found this trial at
2
sites
Houston Methodist Hospital Houston Methodist is comprised of a leading academic medical center in the...
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Texas Children's Hospital Texas Children's Hospital, located in Houston, Texas, is a not-for-profit organization whose...
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