Multi-virus CTLs Expressing CD19 Chimeric Receptors, CD19 Positive Malignancies Post SCT, MULTIPRAT
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Blood Cancer, Lymphoma |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 10/25/2018 |
| Start Date: | April 2009 |
| End Date: | April 2031 |
Phase I Study of the Administration of Multi-Virus-Specific Cytotoxic T Lymphocytes Expressing CD19 Chimeric Receptors for Prophylaxis or Therapy of Relapse of CD19 Positive Malignancies Post Hematopoietic Stem Cell Transplantation
Subjects are having a bone marrow or SCT for either a type of cancer of the blood called
Leukemia or a cancer of the lymph nodes called non- Hodgkin's Lymphoma. Although a transplant
can cure leukemia or lymphoma, some people will relapse. In those who relapse, current
treatment cures only a very small percentage. Although giving patients a dose of donor immune
cells before relapse can prevent relapse of the leukemia or lymphoma, DLI can also cause a
serious complication called graft versus host disease (GVHD). This is a gene transfer
research study using special immune cells which are specific for these cancer cells.
The body has different ways of fighting infection and disease. This study combines 2 of those
ways, antibodies and T cells. T cells (CTLs or cytotoxic T cells) are infection-fighting
blood cells that can kill cells, including tumor cells. Antibodies and T cells have been used
to treat patients with cancers; they have shown promise, but haven't been strong enough to
cure most patients.
The antibody used in this study is called anti-CD19. This antibody sticks to leukemia cells
because of a substance on the outside of these cells called CD19. For this study, the
anti-CD19 antibody has been changed so that instead of floating free in the blood it is now
joined to T cells. When an antibody is joined to a T cell in this way it's called a chimeric
receptor.
In the laboratory, investigators found that T cells that are trained to recognize common
viruses can stay in the blood stream for many years. By joining the anti-CD19 antibody to
CTLs that recognize viruses, they believe that they will also be able to make a cell that can
last a long time in the body, provide protection from viruses, and recognize and kill
leukemia. The CTLs which we will join the anti-CD19 antibody to attack 3 viruses
(trivirus-specific CTLs), CMV, EBV, and adenovirus.
Studies have shown that trivirus-specific CTLs grown from the stem cell donor can be given
safely to transplant recipients and can stop these viruses from causing severe infections.
These CD19 chimeric receptor trivirus specific T cells are an investigational product not
approved by the FDA.
The purpose of this study is to find the biggest dose of chimeric T cells that is safe, to
assess the side effects, to see how long the T cells last and to evaluate whether this
therapy might help prevent infections and relapse in people with CD19+ leukemia or lymphoma
having a SCT.
Leukemia or a cancer of the lymph nodes called non- Hodgkin's Lymphoma. Although a transplant
can cure leukemia or lymphoma, some people will relapse. In those who relapse, current
treatment cures only a very small percentage. Although giving patients a dose of donor immune
cells before relapse can prevent relapse of the leukemia or lymphoma, DLI can also cause a
serious complication called graft versus host disease (GVHD). This is a gene transfer
research study using special immune cells which are specific for these cancer cells.
The body has different ways of fighting infection and disease. This study combines 2 of those
ways, antibodies and T cells. T cells (CTLs or cytotoxic T cells) are infection-fighting
blood cells that can kill cells, including tumor cells. Antibodies and T cells have been used
to treat patients with cancers; they have shown promise, but haven't been strong enough to
cure most patients.
The antibody used in this study is called anti-CD19. This antibody sticks to leukemia cells
because of a substance on the outside of these cells called CD19. For this study, the
anti-CD19 antibody has been changed so that instead of floating free in the blood it is now
joined to T cells. When an antibody is joined to a T cell in this way it's called a chimeric
receptor.
In the laboratory, investigators found that T cells that are trained to recognize common
viruses can stay in the blood stream for many years. By joining the anti-CD19 antibody to
CTLs that recognize viruses, they believe that they will also be able to make a cell that can
last a long time in the body, provide protection from viruses, and recognize and kill
leukemia. The CTLs which we will join the anti-CD19 antibody to attack 3 viruses
(trivirus-specific CTLs), CMV, EBV, and adenovirus.
Studies have shown that trivirus-specific CTLs grown from the stem cell donor can be given
safely to transplant recipients and can stop these viruses from causing severe infections.
These CD19 chimeric receptor trivirus specific T cells are an investigational product not
approved by the FDA.
The purpose of this study is to find the biggest dose of chimeric T cells that is safe, to
assess the side effects, to see how long the T cells last and to evaluate whether this
therapy might help prevent infections and relapse in people with CD19+ leukemia or lymphoma
having a SCT.
The donor gave us blood to make CD19 chimeric receptor trivirus specific T cells in the
laboratory. These cells were grown and frozen for the subject. To make these special T cells
they are grown with stimulator cells. Stimulator cells are also made from the donor's blood
but they are irradiated so that they can no longer grow. Stimulator cells have been infected
with viruses so that they carry proteins from 3 viruses (CMV, adenovirus, and EBV). These
cells are cultured with the T cells so that they can learn to see and attack cells infected
with CMV, EBV and adenovirus.
To get the CD19 antibody to attach to the surface of the T cell, an antibody gene was
inserted 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 injected. Once sufficient numbers of T cells are made,
the investigators freeze the cells and test them to make sure they kill CD19+ tumors cells
and cells infected with CMV, EBV and adenovirus. Once testing is completed the cells will be
ready to give to the subject.
When the subject enrolls on this study, they will be assigned a dose of CD19 chimeric
receptor trivirus specific T cells. The subject will be given an injection of cells into the
vein through an IV line at the assigned dose. The injection will take about 20 minutes.
Investigators will monitor the subject in the clinic after the injection for up to 3 hours.
The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's
Hospital or The Methodist Hospital.
To learn more about the way the CD19 chimeric receptor trivirus specific T cells are working
and how long they last in the body, extra blood will be drawn. The total blood drawn during
this study will not exceed 300 tsp.
For subjects receiving the CTLs for treatment of their disease: If the subject has stable
disease (the tumor did not grow) or there is a reduction in the size of the tumor on imaging
studies or by blood count after the T-cell infusion, the subject can receive up to six
additional doses of the T cells if they wish. After each T-cell infusion, the subject will be
monitored.
Because the subject will have received cells with a new gene in them the subject will be
followed for a total of 15 years to see if there are any long term side effects of gene
transfer.
laboratory. These cells were grown and frozen for the subject. To make these special T cells
they are grown with stimulator cells. Stimulator cells are also made from the donor's blood
but they are irradiated so that they can no longer grow. Stimulator cells have been infected
with viruses so that they carry proteins from 3 viruses (CMV, adenovirus, and EBV). These
cells are cultured with the T cells so that they can learn to see and attack cells infected
with CMV, EBV and adenovirus.
To get the CD19 antibody to attach to the surface of the T cell, an antibody gene was
inserted 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 injected. Once sufficient numbers of T cells are made,
the investigators freeze the cells and test them to make sure they kill CD19+ tumors cells
and cells infected with CMV, EBV and adenovirus. Once testing is completed the cells will be
ready to give to the subject.
When the subject enrolls on this study, they will be assigned a dose of CD19 chimeric
receptor trivirus specific T cells. The subject will be given an injection of cells into the
vein through an IV line at the assigned dose. The injection will take about 20 minutes.
Investigators will monitor the subject in the clinic after the injection for up to 3 hours.
The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's
Hospital or The Methodist Hospital.
To learn more about the way the CD19 chimeric receptor trivirus specific T cells are working
and how long they last in the body, extra blood will be drawn. The total blood drawn during
this study will not exceed 300 tsp.
For subjects receiving the CTLs for treatment of their disease: If the subject has stable
disease (the tumor did not grow) or there is a reduction in the size of the tumor on imaging
studies or by blood count after the T-cell infusion, the subject can receive up to six
additional doses of the T cells if they wish. After each T-cell infusion, the subject will be
monitored.
Because the subject will have received cells with a new gene in them the subject will be
followed for a total of 15 years to see if there are any long term side effects of gene
transfer.
INCLUSION CRITERIA:
1. Any patient regardless of sex or age with CD19+ B-ALL undergoing allogeneic HSCT
(Group A)
OR Any patient regardless of sex or age with CD19+ B-CLL or NHL undergoing allogeneic
HSCT (Group B).
AND
With minimal residual disease (MRD) or relapse post-HSCT (for the phase I dose
escalation)
OR
With no evidence of ALL or CLL/NHL post-HSCT (to be included in the expansion cohort
2. Patients with life expectancy greater than or equal to 6 weeks
3. Patients with a Karnofsky/Lansky score greater than or equal to 50
4. Donor HIV negative
5. Patient or parent/guardian capable of providing informed consent
6. Patients with bilirubin 2x normal or less, AST 3x normal or less, creatinine less than
or equal to 2x normal for age and Hgb greater than 8.0
7. Pulse oximetry of greater than 90% on room air
8. 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.
9. Available allogeneic CD19CAR transduced tri-virus-specific cytotoxic T lymphocytes
with greater than or equal to15% expression of CD19CAR determined by flow-cytometry
and greater than 10% killing of one or more viral antigen pulsed targets in a
cytotoxicity assay at an effector:target ratio of 20:1.*
10. Patients should have been off other investigational antiviral or antitumor therapy for
one month prior to entry in this study.
- Note: Cell dose is based on total cell numbers and not individual antivirus or
antileukemic cell numbers.
EXCLUSION CRITERIA:
1. Severe intercurrent infection
2. Evidence of graft versus host disease >grade II
3. Pregnant or lactating
4. History of hypersensitivity reactions to murine protein-containing products.
5. Currently taking corticosteroids for therapy of GVHD.
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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