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)
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
To prepare the CTLs, 10-60 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 of this study may last for
approximately 18 weeks. The length of time the patient will receive treatment on this study
will depend on how well the chemotherapy treatment works for him or her.
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 10 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 40 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
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 The Methodist Hospital or Texas Children's Hospital. The CTL infusion takes less than
10 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
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The primary endpoint of the study is to evaluate the overall response rate for patients with advanced-stage, relapsed/refractory, EBV positive nasopharyngeal carcinoma after re-induction chemotherapy and immunotherapy.
The overall response rate for patients with advanced-stage, relapsed/refractory, EBV positive nasopharyngeal carcinoma after re-induction chemotherapy (treatment with docetaxel and carboplatin) followed by immunotherapy with EBV-specific Cytotoxic T lymphocytes will be measured. Response rates will be estimated as the percent of patients whose best response is a CR or PR, and a 95% confidence interval will be calculated for the fraction of responses obtained.To measure the overall response rate, disease will be determined by imaging (MRI, CT, and/or PET imaging) 8 weeks after immunotherapy. In addition, per standard of care, disease re-evaluation will continue 3 months during the first year after participation and then as clinically indicated per the patient's primary oncologist.
Chrystal U Louis, MD, MPH
Texas Children's Hospital; Baylor College of Medicine
United States: Food and Drug Administration
|MD Anderson Cancer Center||Houston, Texas 77030-4096|
|Texas Children's Hospital||Houston, Texas|
|The Methodist Hospital||Houston, Texas 77030|