CD19 Chimeric Receptor Expressing T Lymphocytes In B-Cell Non Hodgkin's Lymphoma, ALL & CLL
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Blood Cancer, Lymphoma |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 1/25/2018 |
| Start Date: | February 2009 |
| End Date: | July 2029 |
Phase I Study Of CD19 Chimeric Receptor Expressing T Lymphocytes In B-Cell Non Hodgkin's Lymphoma, Acute Lymphocytic Leukemia, and Chronic Lymphocytic Leukemia
Patients on this study have a type of lymph gland cancer called non-Hodgkin Lymphoma, Acute
Lymphocytic Leukemia, or chronic Lymphocytic Leukemia (these diseases will be referred to as
"Lymphoma" or "Leukemia"). Their Lymphoma or Leukemia has come back or has not gone away
after treatment (including the best treatment known for these cancers). This research study
is a gene transfer study using special immune cells.
The body has different ways of fighting infection and disease. No one way seems perfect for
fighting cancers. This research study combines two different ways of fighting disease,
antibodies and T cells, hoping that they will work together. Antibodies are types of proteins
that protect the body from bacterial and other diseases. T cells, also called T lymphocytes,
are special infection-fighting blood cells that can kill other cells including 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.
T lymphocytes can kill tumor cells but there normally are not enough of them to kill all the
tumor cells. Some researchers have taken T cells from a person's blood, grown more of them in
the laboratory and then given them back to the person.
The antibody used in this study is called anti-CD19. It first came from mice that have
developed immunity to human lymphoma. This antibody sticks to cancer cells because of a
substance on the outside of these cells called CD19. CD19 antibodies have been used to treat
people with lymphoma and Leukemia. For this study anti-CD19 has been changed so that instead
of floating free in the blood it is now joined to the T cells. When an antibody is joined to
a T cell in this way it is called a chimeric receptor.
In the laboratory, investigators have also found that T cells work better if they also put a
protein that stimulates T cells called CD28. Investigators hope that adding the CD28 might
also make the cells last for a longer time in the body.
These CD19 chimeric receptor T cells with C28 T cells are investigational products not
approved by the Food and Drug Administration.
The purpose of this study is to find the biggest dose of chimeric T cells that is safe, to
see how the T cell with this sort of chimeric receptor lasts, to learn what the side effects
are and to see whether this therapy might help people with lymphoma or leukemia.
Lymphocytic Leukemia, or chronic Lymphocytic Leukemia (these diseases will be referred to as
"Lymphoma" or "Leukemia"). Their Lymphoma or Leukemia has come back or has not gone away
after treatment (including the best treatment known for these cancers). This research study
is a gene transfer study using special immune cells.
The body has different ways of fighting infection and disease. No one way seems perfect for
fighting cancers. This research study combines two different ways of fighting disease,
antibodies and T cells, hoping that they will work together. Antibodies are types of proteins
that protect the body from bacterial and other diseases. T cells, also called T lymphocytes,
are special infection-fighting blood cells that can kill other cells including 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.
T lymphocytes can kill tumor cells but there normally are not enough of them to kill all the
tumor cells. Some researchers have taken T cells from a person's blood, grown more of them in
the laboratory and then given them back to the person.
The antibody used in this study is called anti-CD19. It first came from mice that have
developed immunity to human lymphoma. This antibody sticks to cancer cells because of a
substance on the outside of these cells called CD19. CD19 antibodies have been used to treat
people with lymphoma and Leukemia. For this study anti-CD19 has been changed so that instead
of floating free in the blood it is now joined to the T cells. When an antibody is joined to
a T cell in this way it is called a chimeric receptor.
In the laboratory, investigators have also found that T cells work better if they also put a
protein that stimulates T cells called CD28. Investigators hope that adding the CD28 might
also make the cells last for a longer time in the body.
These CD19 chimeric receptor T cells with C28 T cells are investigational products not
approved by the Food and Drug Administration.
The purpose of this study is to find the biggest dose of chimeric T cells that is safe, to
see how the T cell with this sort of chimeric receptor lasts, to learn what the side effects
are and to see whether this therapy might help people with lymphoma or leukemia.
Patients will give us blood to make CD19 CD28 chimeric receptor-T cells in the laboratory.
These cells will be grown and frozen for the patient. To make the T cells investigators take
the blood and stimulate it with growth factors to make the T cells grow. To get the CD19
antibody (with CD28) to attach to the surface of the T cell, they insert the antibody gene
into the T cell. This is done with a virus called a retrovirus that has been made for this
study and will carry the antibody gene into the T cell. This virus also helps us find the T
cells in the blood after they inject them using a special laboratory test. Because the
patients will receive cells with a new gene in them they will be followed for a total of 15
years to see if there are any long term side effects of gene transfer. If the patient cannot
visit the clinic, they may be contacted by the research coordinator or physician.
When the patients enroll on this study, they will be assigned a dose of CD19 CD28 chimeric
receptor-T cells.
For those with intermediate or low grade lymphoma/leukemia: The investigators' studies so far
have shown that the infused T cells may need to receive an extra boost in order to expand
efficiently in the body. Therefore, 2 weeks after T cell infusion, the patient may receive
one injection of a drug called ipilimumab, which they believe will help the T cells grow.
This drug is approved by the FDA to treat certain cancers, such as melanoma, but the dose of
drug used for this study will be lower than those used in those other treatments to avoid
side effects.
Patients will be given an injection of cells into the vein through an IV at the assigned
dose. The injection will take about 10 minutes. Patients will be followed in the clinic after
the injection for up to 3 hours. If after a 4-6 week evaluation period after the infusion,
the patient seems to be experiencing a benefit (confirmed by radiological studies, physical
exam and/or symptoms), they may be able to receive up to three additional doses of the T
cells if they wish. These additional infusions would be at least 4-6 weeks apart and at the
same dose level they received the first time or a lower dose. The treatment will be given by
the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist
Hospital.
To learn more about the way the CD19 CD28 chimeric receptor-T cells are working and how long
they last in the body, extra blood will be drawn.
These cells will be grown and frozen for the patient. To make the T cells investigators take
the blood and stimulate it with growth factors to make the T cells grow. To get the CD19
antibody (with CD28) to attach to the surface of the T cell, they insert the antibody gene
into the T cell. This is done with a virus called a retrovirus that has been made for this
study and will carry the antibody gene into the T cell. This virus also helps us find the T
cells in the blood after they inject them using a special laboratory test. Because the
patients will receive cells with a new gene in them they will be followed for a total of 15
years to see if there are any long term side effects of gene transfer. If the patient cannot
visit the clinic, they may be contacted by the research coordinator or physician.
When the patients enroll on this study, they will be assigned a dose of CD19 CD28 chimeric
receptor-T cells.
For those with intermediate or low grade lymphoma/leukemia: The investigators' studies so far
have shown that the infused T cells may need to receive an extra boost in order to expand
efficiently in the body. Therefore, 2 weeks after T cell infusion, the patient may receive
one injection of a drug called ipilimumab, which they believe will help the T cells grow.
This drug is approved by the FDA to treat certain cancers, such as melanoma, but the dose of
drug used for this study will be lower than those used in those other treatments to avoid
side effects.
Patients will be given an injection of cells into the vein through an IV at the assigned
dose. The injection will take about 10 minutes. Patients will be followed in the clinic after
the injection for up to 3 hours. If after a 4-6 week evaluation period after the infusion,
the patient seems to be experiencing a benefit (confirmed by radiological studies, physical
exam and/or symptoms), they may be able to receive up to three additional doses of the T
cells if they wish. These additional infusions would be at least 4-6 weeks apart and at the
same dose level they received the first time or a lower dose. The treatment will be given by
the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist
Hospital.
To learn more about the way the CD19 CD28 chimeric receptor-T cells are working and how long
they last in the body, extra blood will be drawn.
INCLUSION CRITERIA:
Patients must meet the following eligibility criteria to be included:
1. Recurrent B cell lymphoma or leukemia (ALL or CLL), or newly diagnosed patients unable
to receive or complete standard therapy OR diagnosis of intermediate B cell lymphoma
with a treatment plan that will include high dose therapy and autologous stem cell
transplantation. If a patient is less than 18, the lymphoma/leukemia is highly
aggressive (i.e. lymphoblastic, Burkitt, ALL).
2. Life expectancy of at least 12 weeks
3. Recovered from the toxic effects of all prior chemotherapy before entering this study
4. ANC greater than 500, HgB greater than 8.0
5. Bilirubin less than 3 times the upper limit of normal
6. AST less than 5 times the upper limit of normal
7. Serum creatinine less than 3 times upper limit of normal
8. Pulse oximetry of greater than 90% on room air
9. Karnofsky/Lansky score of greater than 60%
10. Available autologous transduced peripheral blood T-cells with greater than/=15%
expression of CD19CAR determined by flow-cytometry
11. Patients or legal guardians must sign an informed consent indicating that they are
aware this is a research study and have been told of its possible benefits and toxic
side effects. Patients or their guardians will be given a copy of the consent form
12. Sexually active patients must be willing to utilize one of the more effective birth
control methods during the study and for 3 months after the study is concluded. The
male partner should use a condom
EXCLUSION CRITERIA:
1. History of hypersensitivity reactions to murine protein-containing products
2. Pregnant or lactating
3. Tumor in a location where enlargement could cause airway obstruction
4. Currently receiving any investigational agents or have not received any tumor vaccines
within the previous six weeks
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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Houston Methodist Hospital Houston Methodist is comprised of a leading academic medical center in the...
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