Activated T-Cells Expressing 2nd or 3rd Generation CD19-Specific CAR, Advanced B-Cell NHL, ALL, and CLL (SAGAN)
| Status: | Recruiting |
|---|---|
| Conditions: | Blood Cancer, Lymphoma |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any - 75 |
| Updated: | 3/13/2019 |
| Start Date: | February 2014 |
| End Date: | February 2033 |
| Contact: | Carlos A Ramos, MD |
| Email: | caramos@bcm.edu |
| Phone: | 832-824-4817 |
Phase I Study of Activated T-Cells Expressing Second or Third Generation CD19-Specific Chimeric Antigen Receptors for Advanced B-Cell Non-Hodgkin's Lymphoma, Acute Lymphocytic Leukemia and Chronic Lymphocytic Leukemia (SAGAN)
Subjects 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"). The lymphoma or leukemia has come back or has not gone away after
treatment.
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. Both antibodies and T cells have
been used to treat patients with cancer. They have shown promise, but have not been strong
enough to cure most patients.
T cells can kill tumor cells but normally there 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 lymphoma 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, the investigators found that T cells work better if they also add proteins
that stimulate T cells, such as one called CD28. Adding the CD28 makes the cells last longer
in the body but not long enough for them to be able to kill the lymphoma cells. The
investigators believe that if they add an extra stimulating protein, called CD137, the cells
will have a better chance of killing the lymphoma cells.
The investigators are going to see if this is true by putting the CD19 chimeric receptor with
CD28 alone into half of the cells and the CD19 chimeric receptor with CD28 and CD137 into the
other half of the cells. These CD19 chimeric receptor T cells with CD28 and with or without
CD137 are investigational products not approved by the FDA.
The purpose of this study is to find the biggest dose of chimeric T cells that is safe, to
see how long the T cell with each 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"). The lymphoma or leukemia has come back or has not gone away after
treatment.
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. Both antibodies and T cells have
been used to treat patients with cancer. They have shown promise, but have not been strong
enough to cure most patients.
T cells can kill tumor cells but normally there 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 lymphoma 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, the investigators found that T cells work better if they also add proteins
that stimulate T cells, such as one called CD28. Adding the CD28 makes the cells last longer
in the body but not long enough for them to be able to kill the lymphoma cells. The
investigators believe that if they add an extra stimulating protein, called CD137, the cells
will have a better chance of killing the lymphoma cells.
The investigators are going to see if this is true by putting the CD19 chimeric receptor with
CD28 alone into half of the cells and the CD19 chimeric receptor with CD28 and CD137 into the
other half of the cells. These CD19 chimeric receptor T cells with CD28 and with or without
CD137 are investigational products not approved by the FDA.
The purpose of this study is to find the biggest dose of chimeric T cells that is safe, to
see how long the T cell with each 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 the investigators blood to make CD19 CD28 (with and without CD137)
chimeric receptor-T cells in the laboratory. These cells will be grown and frozen. To make
the T cells, investigators will take blood (or blood from a donor) and stimulate it with
growth factors to make the T cells grow. To get the CD19 antibody and CD28 (with or without
CD137) to attach to the surface of the T cell, they will 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 to find the T cells in
the blood after injecting them; in order to tell them apart investigators have made two
viruses that are slightly different because one has CD137. These two viruses can be told
apart by a special laboratory test. Because the patient will receive cells with a new gene in
them, the patient 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, he or she will be
contacted by the research coordinator or physician.
When subjects enroll on this study, they will be assigned a dose of CD19 chimeric receptor-T
cells. Several studies suggest that the infused T cells need room to be able to proliferate
and accomplish their functions and that this may not happen if there are too many other T
cells in circulation.
Because of that, if the subject's level of circulating T cells is relatively high, s/he may
receive one treatment of cyclophosphamide (Cytoxan) and fludarabine if the doctor thinks this
is appropriate. This drug will decrease the numbers of the subject's own T cells before
infusion of the CD19 chimeric receptor T cells. If subject is already receiving chemotherapy,
this may not be needed. The investigators would prefer subjects do not receive other
chemotherapy until 6 weeks after cell infusion but they can do so if their doctor thinks it
is medically necessary.
Patients will be given an injection of cells into the vein through an IV at the assigned
dose. The injection will take about 20 minutes. The investigators will follow them in the
clinic after the injection for up to 3 hours.
If after a 6 week evaluation period after the infusion, the patient seems to be experiencing
a benefit (confirmed by radiological studies, physical exam and/or symptoms), s/he may be
able to receive up to five additional doses of the T cells if s/he wishes. The first repeat
infusion can only take place at least 6 weeks after the first infusion. Any additional
infusions after that would be at least 4 weeks apart. All additional infusions will be at the
same dose level 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.
chimeric receptor-T cells in the laboratory. These cells will be grown and frozen. To make
the T cells, investigators will take blood (or blood from a donor) and stimulate it with
growth factors to make the T cells grow. To get the CD19 antibody and CD28 (with or without
CD137) to attach to the surface of the T cell, they will 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 to find the T cells in
the blood after injecting them; in order to tell them apart investigators have made two
viruses that are slightly different because one has CD137. These two viruses can be told
apart by a special laboratory test. Because the patient will receive cells with a new gene in
them, the patient 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, he or she will be
contacted by the research coordinator or physician.
When subjects enroll on this study, they will be assigned a dose of CD19 chimeric receptor-T
cells. Several studies suggest that the infused T cells need room to be able to proliferate
and accomplish their functions and that this may not happen if there are too many other T
cells in circulation.
Because of that, if the subject's level of circulating T cells is relatively high, s/he may
receive one treatment of cyclophosphamide (Cytoxan) and fludarabine if the doctor thinks this
is appropriate. This drug will decrease the numbers of the subject's own T cells before
infusion of the CD19 chimeric receptor T cells. If subject is already receiving chemotherapy,
this may not be needed. The investigators would prefer subjects do not receive other
chemotherapy until 6 weeks after cell infusion but they can do so if their doctor thinks it
is medically necessary.
Patients will be given an injection of cells into the vein through an IV at the assigned
dose. The injection will take about 20 minutes. The investigators will follow them in the
clinic after the injection for up to 3 hours.
If after a 6 week evaluation period after the infusion, the patient seems to be experiencing
a benefit (confirmed by radiological studies, physical exam and/or symptoms), s/he may be
able to receive up to five additional doses of the T cells if s/he wishes. The first repeat
infusion can only take place at least 6 weeks after the first infusion. Any additional
infusions after that would be at least 4 weeks apart. All additional infusions will be at the
same dose level 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.
Inclusion Criteria:
PROCUREMENT
Referred patients (or respective donors) will initially be consented for procurement of
blood for generation of the transduced ATL. Eligibility criteria at this stage include:
- Diagnosis of recurrent B-cell lymphoma or leukemia (ALL or CLL), or newly diagnosed
patients unable to receive or complete standard therapy OR diagnosis of
relapsed/refractory aggressive B-cell lymphoma with a treatment plan that will include
high dose therapy and autologous stem cell transplantation.
- CD19-positive tumor (result can be pending at this time).
- Age <= 75 years. The first 3 patients treated on the study should be adults (>= 18
years).
- Hgb greater than or equal to 7.0 (can be a transfused value)
- If pheresis required to collect blood:
- Creatinine < 1.5 x upper limit normal
- AST <1.5 × upper limit normal
- PT and APTT <1.5 × upper limit normal
- Informed consent explained to, understood by and signed by patient/guardian (and
donor, where applicable). Patient/guardian given copy of informed consent.
TREATMENT
- Diagnosis of recurrent B-cell lymphoma leukemia (ALL or CLL), or newly diagnosed
patients unable to receive or complete standard therapy OR diagnosis of
relapsed/refractory aggressive B-cell lymphoma with a treatment plan that will include
high dose therapy and autologous stem cell transplantation.
- CD19-positive tumor.
- Age <= 75 years. The first 3 patients treated on the study should be adults (>= 18
years).
- Bilirubin less than 3 times the upper limit of normal.
- AST less than 5 times the upper limit of normal.
- Estimated GFR > 50 mL/min
- Pulse oximetry of > 90% on room air
- Karnofsky or Lansky score of > 60%.
- Recovered from acute toxic effects of prior chemotherapy at least one week before
entering this study. PD1/PDL1 inhibitors will be allowed if medically indicated.
- Available autologous or syngeneic activated peripheral blood T cell products (CD28ζ
and CD28/CD137ζ) with more than or equal to 15% expression of CD19.CAR determined by
flow cytometry.
- Life expectancy of greater than 12 weeks.
- Sexually active patients must be willing to utilize one of the more effective birth
control methods during the study and for 6 months after the study is concluded. The
male partner should use a condom.
- 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.
Exclusion Criteria:
PROCUREMENT
- Active infection requiring antibiotics.
- No history of other cancer (except non-melanoma skin cancer or in situ breast cancer
or cervix cancer) unless the tumor was successfully treated with curative intent at
least 2 years before trial entry.
TREATMENT
- Currently receiving any investigational agents or received any tumor vaccines within
the previous 6 weeks. (Note treatment with PD1/PDL1 inhibitors is allowed.)
- History of hypersensitivity reactions to murine protein-containing products.
- Pregnant or lactating.
- Tumor in a location where enlargement could cause airway obstruction.
- Active infection with HIV or HTLV.
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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