Carboplatin and Docetaxel Followed by Epstein-Barr Virus Cytotoxic T Lymphocytes
| Status: | Completed |
|---|---|
| Conditions: | Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 10 - Any |
| Updated: | 8/19/2017 |
| Start Date: | November 2009 |
| End Date: | July 2015 |
Phase II Study of Carboplatin and Docetaxel Followed by Epstein-Barr Virus Cytotoxic T Lymphocytes in Patients With Refractory/Relapsed EBV-positive Nasopharyngeal Carcinoma(CADEN)
Patients have a type of cancer called nasopharyngeal carcinoma (NPC) that has either come
back or not gone away after the best known standard treatments.
Most patients that respond to chemotherapy once their NPC tumors have come back have been
treated with a platinum-based medication like cisplatin. However, since many patients are
given cisplatin during their initial treatment for NPC, in this study, they will be treated
with another platinum-based chemotherapy medicine that has been used in patients with NPC
called carboplatin. In this study, carboplatin will be used in combination with another drug
called docetaxel. Other studies in patients with advanced head and neck cancer have shown
that docetaxel can cause tumors to respond better and allow patients to survive longer when
added to the standard treatments for those diseases.
Some patients with NPC show evidence of infection with the virus that causes infectious
mononucleosis, known as the Epstein Barr virus (EBV), before or at the time of their cancer
diagnosis. EBV is found in the cancer cells of almost all patients with advanced stage
disease, suggesting that it may play a role in causing NPC. Previously, patients have been
treated with high-risk NPC using EBV-specific cytotoxic T cells. These cells are grown in the
laboratory and taught to recognize and attack EBV infected cells. In the past, patients were
either given the cells alone or just after they had received a medication to briefly lower
their white blood cell count. In both cases, many patients had their tumors shrink and in
some cases completely disappear after being treated with these EBV-specific cytotoxic T
cells.
Investigators have now decided to look at how patients with NPC and their tumors respond to
the treatment combination of chemotherapy and EBV-CTL. Patients are being asked to
participate in this study since the NPC tumor is associated with EBV and has either come back
or not responded to standard treatment. This combination of chemotherapy and EBV-CTLs is an
investigational treatment not approved by the Food and Drug Administration.
The purpose of this study is to see how relapsed or refractory, EBV-associated NPC tumors
respond when treated with carboplatin and docetaxel followed by EBV-CTL.
back or not gone away after the best known standard treatments.
Most patients that respond to chemotherapy once their NPC tumors have come back have been
treated with a platinum-based medication like cisplatin. However, since many patients are
given cisplatin during their initial treatment for NPC, in this study, they will be treated
with another platinum-based chemotherapy medicine that has been used in patients with NPC
called carboplatin. In this study, carboplatin will be used in combination with another drug
called docetaxel. Other studies in patients with advanced head and neck cancer have shown
that docetaxel can cause tumors to respond better and allow patients to survive longer when
added to the standard treatments for those diseases.
Some patients with NPC show evidence of infection with the virus that causes infectious
mononucleosis, known as the Epstein Barr virus (EBV), before or at the time of their cancer
diagnosis. EBV is found in the cancer cells of almost all patients with advanced stage
disease, suggesting that it may play a role in causing NPC. Previously, patients have been
treated with high-risk NPC using EBV-specific cytotoxic T cells. These cells are grown in the
laboratory and taught to recognize and attack EBV infected cells. In the past, patients were
either given the cells alone or just after they had received a medication to briefly lower
their white blood cell count. In both cases, many patients had their tumors shrink and in
some cases completely disappear after being treated with these EBV-specific cytotoxic T
cells.
Investigators have now decided to look at how patients with NPC and their tumors respond to
the treatment combination of chemotherapy and EBV-CTL. Patients are being asked to
participate in this study since the NPC tumor is associated with EBV and has either come back
or not responded to standard treatment. This combination of chemotherapy and EBV-CTLs is an
investigational treatment not approved by the Food and Drug Administration.
The purpose of this study is to see how relapsed or refractory, EBV-associated NPC tumors
respond when treated with carboplatin and docetaxel followed by EBV-CTL.
A blood sample will be obtained to start making the CTLs before the patient begins
chemotherapy. The patients EBV-specific T cells will be grown while the patient is being
treated with chemotherapy and given back to the patient after their chemotherapy is
completed.
To prepare the CTLs, 60-70 cc of blood will be taken from the patient. The amount of blood
collected depends on their size and weight, no more than 3 cc of blood per kg of body weight
will be collected at any one time.
This blood will be used to grow an EBV-infected B-cell line and then a T-cell line. B cells
and T cells are types of white blood cells that help fight infections in the body. After
growing T cells in the laboratory, these cells will be stimulated with EBV infected B cells.
The B cells have been treated with radiation so they cannot grow; however, they can provide
the stimulation that will train the T cells to recognize and kill EBV infected cells.
The generation of EBV-CTL requires the use of a special cell line, called lymphoblastoid cell
line, which will be made from the blood by infecting cells with EBV. Once the LCLs are made,
the T cells will be repeatedly stimulate with the LCLs to make EBV-CTL.
The CTLs will then be tested to make sure they kill the EBV infected cells before they are
given back to the patient. If the number of CTLs produced is low, investigators may need to
obtain additional blood samples to make these cells.
Because the patients cells are being grown in the laboratory, blood will have to be taken to
test for infectious viruses such as hepatitis and HIV and patients will also have to fill in
a questionnaire that is given to standard blood donors.
EXPECTED LENGTH OF STUDY The chemotherapy treatment portion is planned as 4 cycles of
chemotherapy given every 3 weeks. Up to an additional 2 cycles of chemotherapy may be given
if the EBV-CTL product is not available after the initial 4 cycles.
If the patient has been able to complete at least 4 cycles of chemotherapy and the EBV-CTL
are ready for infusion,then the cells will be given back to the patient. The infusion of the
T cells will last about 1 to 5 minutes after the patient has been pretreated with one dose of
Tylenol and Benadryl.
The patient will have another disease re-evaluation 8 weeks after the first EBV-CTL
injection. Based upon the patient's response to the first infusion, the patient may receive
extra doses of cells if they are available. These would be given every 1.5-3 months. If the
patient has additional injections of cells, this will require an additional disease
re-evaluation 8 weeks after each infusion.
To learn more about the way the EBV-CTLS are working and how long they last in the body,
10-60 mls of blood will be taken before and after each infusion. Up to 60 ml of blood will
also be drawn before each cycle of chemotherapy that occurs at Week 1, Week 4, Week 7, Week
10 before the T cell infusion and then at Weeks 1, 2, 4, 6 and 8 weeks after infusion, and
then again at the follow-up visits 5, 8, and 11-12 months after infusion. This blood will be
used to look at the immune response to the patient's cancer. If the patient only has one
EBV-CTL infusion, up to 108 teaspoons of blood will be drawn to allow for evaluation of his
or her response to treatment; however, the total amount of blood collected on this study will
depend on the total number of EBV-CTL infusions that the patient has.
The patient and his/her response to therapy will be followed for at least 1 year after
treatment on this study ends.
STUDY TREATMENT While the cells are being grown, the patient will be started on chemotherapy
in order to shrink the size and/or amount of his/her tumor.
The patient will be treated with a combination of docetaxel and carboplatin chemotherapy. The
chemotherapy will be given outpatient over several hours. Docetaxel can cause the body to
hold on to extra fluid (fluid retention). This side effect can be prevented in most people if
they take a small steroid dose before and after docetaxel is given. Therefore, the night
before and on the morning chemotherapy is to start, the patient will take a steroid called
dexamethasone by mouth.
Once the patient gets to clinic, he/she will be given a dose of docetaxel and then a dose of
carboplatin. Each of these medications will be given into the vein after an IV is placed or
into the central line. The patient will then take the last dose of dexamethasone before going
to bed that night. The patient will receive chemotherapy treatment once every 21 days as long
as the patient's blood counts and laboratory tests have returned to an acceptable level. The
patient will have a re-evaluation of his/her disease with imaging scans and laboratory tests
after the second round of chemotherapy. If the patient's tumor has not gotten worse and/or
has not had severe side effects from the chemotherapy, the patient will be treated with 2 to
4 additional rounds of chemotherapy while we are waiting for the EBV-CTLs to be finished.
The combination of chemotherapy agents used in this study might cause the patient's white
blood cells to be low. If they are low for a long period of time or the patient develop a
serious infection while they are low, her/she may be given an extra medication called
Granulocyte colony-stimulating factor (GCSF). GCSF helps to stimulate the production of white
blood cells. However, it is anticipated that most people on the study will not require GCSF.
Once the EBV-CTLs are ready and the patient has recovered from the last round of
chemotherapy, the EBV-CTL infusion will be scheduled. The CTL infusion will take place at
either Houston Methodist Hospital or Texas Children's Hospital. The CTL infusion takes about
1 to 5 minutes, but patients are typically monitored for up to 4 hours after the infusion to
make sure that he/she does not have a reaction to the cells.
END OF TREATMENT AND FOLLOW-UP
The patient will have a number of tests and procedures as part of follow up to treatment.
These tests will be used to watch for improvements in tumor size, monitor for side effects
from the treatment, evaluate how the T cells are working, and look for any signs that the
cancer has come back. The patient's will have a physical exam and standard lab tests,
including blood tests, and imaging studies about every 3 months during the first year after
treatment.
chemotherapy. The patients EBV-specific T cells will be grown while the patient is being
treated with chemotherapy and given back to the patient after their chemotherapy is
completed.
To prepare the CTLs, 60-70 cc of blood will be taken from the patient. The amount of blood
collected depends on their size and weight, no more than 3 cc of blood per kg of body weight
will be collected at any one time.
This blood will be used to grow an EBV-infected B-cell line and then a T-cell line. B cells
and T cells are types of white blood cells that help fight infections in the body. After
growing T cells in the laboratory, these cells will be stimulated with EBV infected B cells.
The B cells have been treated with radiation so they cannot grow; however, they can provide
the stimulation that will train the T cells to recognize and kill EBV infected cells.
The generation of EBV-CTL requires the use of a special cell line, called lymphoblastoid cell
line, which will be made from the blood by infecting cells with EBV. Once the LCLs are made,
the T cells will be repeatedly stimulate with the LCLs to make EBV-CTL.
The CTLs will then be tested to make sure they kill the EBV infected cells before they are
given back to the patient. If the number of CTLs produced is low, investigators may need to
obtain additional blood samples to make these cells.
Because the patients cells are being grown in the laboratory, blood will have to be taken to
test for infectious viruses such as hepatitis and HIV and patients will also have to fill in
a questionnaire that is given to standard blood donors.
EXPECTED LENGTH OF STUDY The chemotherapy treatment portion is planned as 4 cycles of
chemotherapy given every 3 weeks. Up to an additional 2 cycles of chemotherapy may be given
if the EBV-CTL product is not available after the initial 4 cycles.
If the patient has been able to complete at least 4 cycles of chemotherapy and the EBV-CTL
are ready for infusion,then the cells will be given back to the patient. The infusion of the
T cells will last about 1 to 5 minutes after the patient has been pretreated with one dose of
Tylenol and Benadryl.
The patient will have another disease re-evaluation 8 weeks after the first EBV-CTL
injection. Based upon the patient's response to the first infusion, the patient may receive
extra doses of cells if they are available. These would be given every 1.5-3 months. If the
patient has additional injections of cells, this will require an additional disease
re-evaluation 8 weeks after each infusion.
To learn more about the way the EBV-CTLS are working and how long they last in the body,
10-60 mls of blood will be taken before and after each infusion. Up to 60 ml of blood will
also be drawn before each cycle of chemotherapy that occurs at Week 1, Week 4, Week 7, Week
10 before the T cell infusion and then at Weeks 1, 2, 4, 6 and 8 weeks after infusion, and
then again at the follow-up visits 5, 8, and 11-12 months after infusion. This blood will be
used to look at the immune response to the patient's cancer. If the patient only has one
EBV-CTL infusion, up to 108 teaspoons of blood will be drawn to allow for evaluation of his
or her response to treatment; however, the total amount of blood collected on this study will
depend on the total number of EBV-CTL infusions that the patient has.
The patient and his/her response to therapy will be followed for at least 1 year after
treatment on this study ends.
STUDY TREATMENT While the cells are being grown, the patient will be started on chemotherapy
in order to shrink the size and/or amount of his/her tumor.
The patient will be treated with a combination of docetaxel and carboplatin chemotherapy. The
chemotherapy will be given outpatient over several hours. Docetaxel can cause the body to
hold on to extra fluid (fluid retention). This side effect can be prevented in most people if
they take a small steroid dose before and after docetaxel is given. Therefore, the night
before and on the morning chemotherapy is to start, the patient will take a steroid called
dexamethasone by mouth.
Once the patient gets to clinic, he/she will be given a dose of docetaxel and then a dose of
carboplatin. Each of these medications will be given into the vein after an IV is placed or
into the central line. The patient will then take the last dose of dexamethasone before going
to bed that night. The patient will receive chemotherapy treatment once every 21 days as long
as the patient's blood counts and laboratory tests have returned to an acceptable level. The
patient will have a re-evaluation of his/her disease with imaging scans and laboratory tests
after the second round of chemotherapy. If the patient's tumor has not gotten worse and/or
has not had severe side effects from the chemotherapy, the patient will be treated with 2 to
4 additional rounds of chemotherapy while we are waiting for the EBV-CTLs to be finished.
The combination of chemotherapy agents used in this study might cause the patient's white
blood cells to be low. If they are low for a long period of time or the patient develop a
serious infection while they are low, her/she may be given an extra medication called
Granulocyte colony-stimulating factor (GCSF). GCSF helps to stimulate the production of white
blood cells. However, it is anticipated that most people on the study will not require GCSF.
Once the EBV-CTLs are ready and the patient has recovered from the last round of
chemotherapy, the EBV-CTL infusion will be scheduled. The CTL infusion will take place at
either Houston Methodist Hospital or Texas Children's Hospital. The CTL infusion takes about
1 to 5 minutes, but patients are typically monitored for up to 4 hours after the infusion to
make sure that he/she does not have a reaction to the cells.
END OF TREATMENT AND FOLLOW-UP
The patient will have a number of tests and procedures as part of follow up to treatment.
These tests will be used to watch for improvements in tumor size, monitor for side effects
from the treatment, evaluate how the T cells are working, and look for any signs that the
cancer has come back. The patient's will have a physical exam and standard lab tests,
including blood tests, and imaging studies about every 3 months during the first year after
treatment.
INCLUSION CRITERIA:
- Nasopharyngeal Carcinoma in first or subsequent relapse or with primary refractory
disease in whom the EBV-genome or antigens have been demonstrated in tissue biopsy
samples
- Age 10 years or older
- Life expectancy of 8 weeks or more
- Karnofsky or Lansky score of 50 or more
- Normal bilirubin level (per institutional standard)
- AST and ALT 1.5 x or less upper limit of normal
- Alk Phos level less than 2.5 x upper limit of normal
- ANC greater than 1500 cells/ul
- Hgb 8.0 or greater
- Platelets 100,000 cells/ul or more
- Creatinine 2 x or less ULN or GFR 50 ml/min/1.73 m2 or more
- Women of child-bearing potential must take/use effective birth control while
participating in the study.
EXCLUSION CRITERIA:
- Due to the unknown effects of this therapy on a fetus, pregnant women will be excluded
from this research.
- Prior allergic reaction to the study drugs used in this protocol or other drugs
formulated with polysorbate 80.
- Known HIV positive subjects since treatment may be significantly immunosuppressive
- Women who are breast-feeding
- Severe intercurrent infection
- Patients, who in the opinion of the investigator, may not be able to comply with the
safety monitoring requirements of the study
We found this trial at
3
sites
Click here to add this to my saved trials
Houston Methodist Hospital Houston Methodist is comprised of a leading academic medical center in the...
Click here to add this to my saved trials
Texas Children's Hospital Texas Children's Hospital, located in Houston, Texas, is a not-for-profit organization whose...
Click here to add this to my saved trials