Her2 Chimeric Antigen Receptor Expressing T Cells in Advanced Sarcoma
| Status: | Recruiting |
|---|---|
| Conditions: | Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 1/19/2019 |
| Start Date: | February 11, 2010 |
| End Date: | July 2032 |
| Contact: | MEENAKSHI G HEGDE, MD |
| Email: | mghegde@txch.org |
| Phone: | 832-824-4840 |
Administration of Her2 Chimeric Antigen Receptor Expressing T Cells for Subjects With Advanced Sarcoma (HEROS)
Patients have a type of cancer called sarcoma. Because there is no standard treatment for the
patients cancer at this time or because the currently used treatments do not work fully in
all cases, patients are being asked to volunteer to take part in a gene transfer research
study using special immune cells. This research study combines two different ways of fighting
disease: antibodies and T cells. Antibodies are proteins that protect the body from diseases
caused by germs or toxic substances. They work by binding those germs or substances, which
stops them from growing or exerting their toxic effects. T cells, also called T lymphocytes,
are special infection-fighting blood cells that can kill other cells, including tumor cells
or cells that are infected with germs. Both antibodies and T cells have been used to treat
patients with cancers: they both have shown promise, but have not been strong enough to cure
most patients. We have found from previous research that we can put a new gene into T cells
that will make them recognize cancer cells and kill them. We now want to see if we can put a
new gene in these cells that will let the T cells recognize and kill sarcoma cells. The new
gene that we will put in makes an antibody specific for HER2 (Human Epidermal Growth Factor
Receptor 2) that binds to sarcoma cells. In addition it contains CD28, which stimulated T
cells and make them last longer. In other clinical studies using T cells, some investigators
found that giving chemotherapy before the T cell infusion can improve the amount of time the
T cells stay in the body and therefore the effect the T cells can have. Giving chemotherapy
before a T cell infusion is called lymphodepletion since the chemotherapy is specifically
chosen to decrease the number of lymphocytes in the body. Decreasing the number of patient's
lymphocytes first should allow the T cells we infuse to expand and stay longer in your body,
and potentially kill cancer cells more effectively. We will use fludarabine or the
combination of cyclophosphamide and fludarabine as the chemotherapy agents for
lymphodepletion. Cyclophosphamide and fludarabine are the chemotherapy agents most commonly
used for lymphodepletion in immunotherapy clinical trials. The purpose of this study is to
find the largest safe dose of chimeric T cells, and to see whether this therapy might help
patients with sarcoma. Another purpose is to see if it is safe to give HER2-CD28 T cells
after lymphodepleting chemotherapy.
patients cancer at this time or because the currently used treatments do not work fully in
all cases, patients are being asked to volunteer to take part in a gene transfer research
study using special immune cells. This research study combines two different ways of fighting
disease: antibodies and T cells. Antibodies are proteins that protect the body from diseases
caused by germs or toxic substances. They work by binding those germs or substances, which
stops them from growing or exerting their toxic effects. T cells, also called T lymphocytes,
are special infection-fighting blood cells that can kill other cells, including tumor cells
or cells that are infected with germs. Both antibodies and T cells have been used to treat
patients with cancers: they both have shown promise, but have not been strong enough to cure
most patients. We have found from previous research that we can put a new gene into T cells
that will make them recognize cancer cells and kill them. We now want to see if we can put a
new gene in these cells that will let the T cells recognize and kill sarcoma cells. The new
gene that we will put in makes an antibody specific for HER2 (Human Epidermal Growth Factor
Receptor 2) that binds to sarcoma cells. In addition it contains CD28, which stimulated T
cells and make them last longer. In other clinical studies using T cells, some investigators
found that giving chemotherapy before the T cell infusion can improve the amount of time the
T cells stay in the body and therefore the effect the T cells can have. Giving chemotherapy
before a T cell infusion is called lymphodepletion since the chemotherapy is specifically
chosen to decrease the number of lymphocytes in the body. Decreasing the number of patient's
lymphocytes first should allow the T cells we infuse to expand and stay longer in your body,
and potentially kill cancer cells more effectively. We will use fludarabine or the
combination of cyclophosphamide and fludarabine as the chemotherapy agents for
lymphodepletion. Cyclophosphamide and fludarabine are the chemotherapy agents most commonly
used for lymphodepletion in immunotherapy clinical trials. The purpose of this study is to
find the largest safe dose of chimeric T cells, and to see whether this therapy might help
patients with sarcoma. Another purpose is to see if it is safe to give HER2-CD28 T cells
after lymphodepleting chemotherapy.
Because the cells have 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.
When the patient is enrolled on this study, they will be assigned a dose of HER2-CD28 T
cells. Depending on which dose level they are assigned, they will receive one of the
following:
HER2-CD28 T cells and fludarabine (patient will receive fludarabine for 5 days followed by
injection of HER2-CD28 T cells)
OR
HER2-CD28 T cells, fludarabine and cyclophosphamide (patient will receive fludarabine and
cyclophosphamide for 2 days, fludarabine alone for an additional 3 days, and 2 days of rest
before receiving the HER2-CD28 T cells.).
The HER2-CD28 T cells will be given into the vein through an IV line. 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.
Each patient will be followed for 6 weeks after the T-cell infusion for evaluation of
toxicity. They will have standard tests and procedures as well as research blood draws.
If the patient has stable disease (the tumor did not grow) or there is a reduction in the
size of the tumor on imaging studies after the T-cell infusion, they can receive additional
doses of the T cells at 6 to 12 weeks intervals. For the first two subsequent HER2-specific
T-cell infusions, patients will be able to receive additional lymphodepleting chemotherapy
according to their dose levels.
years to see if there are any long term side effects of gene transfer.
When the patient is enrolled on this study, they will be assigned a dose of HER2-CD28 T
cells. Depending on which dose level they are assigned, they will receive one of the
following:
HER2-CD28 T cells and fludarabine (patient will receive fludarabine for 5 days followed by
injection of HER2-CD28 T cells)
OR
HER2-CD28 T cells, fludarabine and cyclophosphamide (patient will receive fludarabine and
cyclophosphamide for 2 days, fludarabine alone for an additional 3 days, and 2 days of rest
before receiving the HER2-CD28 T cells.).
The HER2-CD28 T cells will be given into the vein through an IV line. 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.
Each patient will be followed for 6 weeks after the T-cell infusion for evaluation of
toxicity. They will have standard tests and procedures as well as research blood draws.
If the patient has stable disease (the tumor did not grow) or there is a reduction in the
size of the tumor on imaging studies after the T-cell infusion, they can receive additional
doses of the T cells at 6 to 12 weeks intervals. For the first two subsequent HER2-specific
T-cell infusions, patients will be able to receive additional lymphodepleting chemotherapy
according to their dose levels.
INCLUSION CRITERIA:
Procurement Eligibility:
1. Diagnosis of refractory HER2-positive sarcoma or metastatic HER2-positive
osteosarcoma, not treatable by surgical resection.
2. Karnofsky/Lansky score of 50 or greater
3. Informed consent explained to, understood by and signed by patient/guardian.
Patient/guardian given copy of informed consent.
Treatment Eligibility:
1. Diagnosis of refractory HER2-positive sarcoma or metastatic HER2-positive sarcoma, not
treatable by surgical resection and with disease progression after receiving at least
one prior systemic therapy.
2. Recovered from acute toxic effects of all prior cytotoxic chemotherapy at least 4
weeks before entering this study. PD1/PDL1 inhibitors will be allowed to continue
during treatment if medically indicated.
3. Normal ECHO (Left ventricular ejection fraction (LVEF) has to be within normal,
institutional limits)
4. Life expectancy 6 weeks or greater
5. Karnofsky/Lansky score of 50 or greater
6. Bilirubin 3x or less, AST 5x or less, Serum creatinine 2x upper limit of normal or
less, Hgb 7.0 g/dl or greater, WBC greater than 2,000/ul, ANC greater than 1,000/ul,
platelets greater than 100,000/ul. Creatinine clearance is needed for patients with
creatinine greater than 1.5 times upper limit of normal.
7. Pulse oximetry of 90% or greater 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. Male partner should use a condom
9. Available autologous transduced T lymphocytes with 15% or more expression of HER2 CAR
as determined by flow-cytometry and killing of HER2-positive targets 20 % or greater
in cytotoxicity assay.
10. Informed consent explained to, understood by and signed by patient/guardian.
Patient/guardian given copy of informed consent
EXCLUSION CRITERIA:
At time of Procurement:
1. Known HIV positivity
2. Severe previous toxicity from cyclophosphamide or fludarabine
At time of Treatment:
1. Severe intercurrent infection
2. Known HIV positivity
3. Pregnant or lactating
4. History of hypersensitivity reactions to murine protein-containing products
5. Severe previous toxicity from cyclophosphamide or fludarabine
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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