Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT02065362 |
| Other study ID # |
33954: RESIST-NPC |
| Secondary ID |
P01CA094237 |
| Status |
Active, not recruiting |
| Phase |
Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
February 2015 |
| Est. completion date |
February 2033 |
Study information
| Verified date |
December 2023 |
| Source |
Baylor College of Medicine |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Patients have nasopharyngeal carcinoma (NPC). This study is a gene transfer research study
using special immune cells.
Most patients with NPC show evidence of infection with the virus that causes infectious
mononucleosis Epstein Barr virus (EBV) before or at the time of their diagnosis. EBV is found
in the cancer cells of almost all patients with advanced stage NPC, suggesting that it may
play a role in causing the disease. The cancer cells infected by EBV are able to hide from
the body's immune system and escape destruction. We want to see if special white blood cells,
called T cells, that have been trained to recognize and kill special parts of EBV infected
cells can survive in patient's blood and affect the tumor.
We already have given EBV-specific cytotoxic T cells to 30 patients with active NPC and have
seen anti-tumor activity in 14 of 30 patients. We are now trying to find out if we can
improve this treatment.
First, we want to give T cells where more of the cells recognize at least two of the four EBV
proteins expressed on NPC cells. We call these cells NPC-specific cytotoxic T cells.
Second, we found that T cells work better if we add a receptor to the T cells called DNR
(Dominant Negative Receptor). DNR makes T cells resistant to TGFbeta, a factor secreted by
cancer cells that helps them escape being killed by the immune system. In this study we will
therefore place the DNR gene into NPC-specific T cells (DNR.NPC-specific T cells).
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 their body, and potentially kill cancer
cells more effectively.
The chemotherapy we will use for lymphodepletion is a combination of cyclophosphamide and
fludarabine. Cyclophosphamide and fludarabine are the chemotherapy agents most commonly used
for lymphodepletion in immunotherapy clinical trials.
Description:
Blood will be collected from the patient to make LMP/BARF1/EBNA1 (NPC)-specific T cells. To
grow NPC-specific T cells we have to use special cells called antigen-presenting cells, which
train the patient's T cells to be NPC specific. Antigen presenting cells, so called monocytes
or dendritic cells, will be grown/isolated from the patient's blood. In addition, we use a
cell line called K562 as antigen-presenting cells that has had genes put inside it, which
encourage the patient's T cells to grow. K562 cells are cancer cells. As such, if injected
they could cause cancer. The cells have been treated with radiation so they cannot grow.
These antigen-presenting cells are coated with a specially produced mixture of LMP, EBNA1 and
BARF protein fragments called peptides. These coated antigen-presenting cells are then used
to generate the patient's NPC-specific T cells in the presence of growth factors. To get the
DNR to attach to the surface of these NPC-specific T Cells, we also inserted the DNR gene
into the NPC-specific T cells (DNR.NPC-specific T cells). This is done with a virus called a
retrovirus that has been made for this study. This virus will carry the DNR gene into the
cells.
Once we have made sufficient numbers of DNR.NPC-specific T cells we will freeze the cells and
test them to make sure they recognize EBV proteins present in NPC.
Patients will get treated with 1) either two doses of DNR.NPC-specific T cells (the second
dose will be given 2 weeks after the first dose) or 2)cyclophosphamide and fludarabine for 3
days before receiving the DNR.NPC-specific T cells.
The cyclophosphamide and fludarabine will be given through a needle inserted into a vein or
patient's port-a-cath).
The T cells will be thawed and infused through a central line, or through a vein in the
patient's arm over 1 to 10 minutes. Patients will be followed in the clinic after the
infusion for 1 to 4 hours.
All of the treatments will be given by the Center for Cell and Gene Therapy at Texas
Children's Hospital or Houston Methodist Hospital.
Medical tests before treatment:
Before being treated, the patient will receive a series of standard medical tests:
Physical exam Imaging Study Blood tests to measure blood cells, kidney and liver function
Measurements of the tumor by routine imaging studies. We will use the imaging study that was
used before to follow the patient's tumor: Computer Tomogram (CT), Magnetic Resonance Imaging
(MRI), or Positron Emission Tomography (PET/CT)
Medical tests during and after treatment:
The patient will receive standard medical tests when they are getting the infusions and
after:
Physical exams Blood tests to measure blood cells, kidney and liver function Imaging study 8
weeks after the 1st T-cell infusion(for patients receiving only DNR.NPC-specific T cells ) or
Imaging study 6 weeks after the T-cell infusion (for patients receiving fludarabine and
cyclophosphamide before DNR.NPC-specific T-cell infusion).
To learn more about the way the DNR.NPC-specific T cells are working and how long they last
in the body, an extra 60ml or 3ml/kg of body weight of blood (whichever is less) will be
taken pre-chemotherapy (for the patients receiving chemotherapy), on the day of the T-cell
infusion (before and at the end of the T-cell infusion), 1, 2, 3, 4. 6, and 8 weeks( the last
time point only for patients receiving DNR.NPC-specific T-cells only) after the T-cell
infusion and every 3 months for 1 year, every 6 months for 4 years, then yearly for a total
of 15 years. One additional blood sample might be drawn 3 to 4 days post the 1st T-cell
infusion; this is optional. This volume is considered safe, but may be decreased if the
patient is anemic. In addition to the blood tests, the patient will receive 2 imaging studies
as stated above.
During the time points listed above, if the DNR.NPC-specific T cells are found in patient's
blood at a certain amount an extra 5ml of blood may need to be collected for additional
testing.
