Clinical Trial Details
— Status: Active, not recruiting
Administrative data
NCT number |
NCT01333046 |
Other study ID # |
H-27471-TACTAL |
Secondary ID |
TACTAL2P50CA1267 |
Status |
Active, not recruiting |
Phase |
Phase 1
|
First received |
|
Last updated |
|
Start date |
January 2012 |
Est. completion date |
September 27, 2027 |
Study information
Verified date |
May 2024 |
Source |
Baylor College of Medicine |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Patients have a type of lymph gland disease called Hodgkin or non-Hodgkin lymphoma which has
come back, or may come back, or has not gone away after treatment, including the standard
treatment known for these diseases. This a research study using special immune system cells
called tumor associated antigen (TAA)-specific cytotoxic T lymphocytes, a new experimental
therapy.
This sort of therapy has been used previously to treat Hodgkin or non-Hodgkin lymphomas that
show proof of infection with Epstein-Barr virus (EBV), the virus that causes infectious
mononucleosis ("mono" or the "kissing disease"). EBV is found in cancer cells of up to half
of all patients with Hodgkin's and non-Hodgkin lymphoma. This suggests that it may play a
role in causing lymphoma. The cancer cells infected by EBV are able to hide from the body's
immune system and escape being killed. Investigators tested whether special white blood
cells, called T cells, that were trained to kill EBV-infected cells could affect these
tumors, and in many patients it was found that giving these trained T cells caused a complete
or partial response.
However, many patients do not have EBV in their lymphoma cells; therefore investigators now
want to test whether it is possible to direct these special T cells against other types of
proteins on the tumor cell surface with similar promising results. The proteins that will be
targeted in this study are called tumor associated antigens (TAAs) - these are cell proteins
that are specific to the cancer cell, so they either do not show or show up in low quantities
on normal human cells.
In this study, we will target five TAAs which commonly show on lymphoma, called: NY-ESO-1,
MAGEA4, PRAME, Survivin and SSX. This will be done by using special types of T cells called
cytotoxic T lymphocytes (CTLs) generated in the lab.
In addition, some adult patients will receive a drug called azacytidine before giving the T
cells. We hope that the combination helps the T cells work better.
Description:
The patient will give blood to make TAA-specific cytotoxic T cells in the lab. These cells
will be grown and frozen. If the TAA-specific cytotoxic T cells can be made, the time from
collection of the blood to manufacture of T cells for administration to the patient is about
1 to 2 months.
There are 4 stages of this study: an antigen-escalation phase, a dose-escalation stage, aza
stage and pediatric patients stage.
The antigen-escalation phase will be first. Patients will receive TAA-specific T cells
targeting first 1 and then 2 TAAs. Once this schedule proves safe, the next group of patients
will receive TAA-specific T cells targeting first 2 and then 3 TAAs. This process will
continue until all 4 levels are studied. This means that the final cohort of patients will
receive TAA-specific T cells targeting first 4 and then 5 TAAs. If the side-effects are too
severe, the number of TAAs being targeted will be lowered or the T cell injections will be
stopped. Each patient will receive 2 infusions at the same dose 28 days apart
After the antigen-escalation phase, the dose-escalation phase will begin. Patients will be
started on the lowest dose (1 of 3 different levels) of T cells. Once that dose schedule
proves safe, the next group of patients will be started at a higher dose. This process will
continue until all 3 dose levels are studied. If the side-effects are too severe, the dose
will be lowered or the T cell injections will be stopped. Each patient will receive 2
infusions at the same dose 14 days apart
After the dose escalation stage, adult patients will be enrolled on the aza stage where they
will receive the drug aza followed by two infusions of T cells on dose level 2. Patients will
be given 3 cycles of aza (administered daily through a vein for 5 days, every 28 days)
followed by 2 doses of multiTAA-specific T cells administered 14 days apart. Before the
patient is given the aza they will be given a drug to help prevent nausea and vomiting.
On the pediatric stage, pediatric patients will receive 2 infusions of T cells on dose level
2. The T cells will be given 14 days apart.
The cells will be injected by IV over 10 minutes. The patients may be pre-treated with
acetaminophen (Tylenol) and diphenhydramine (Benadryl). Acetaminophen (Tylenol) and
diphenhydramine (Benadryl) are given to prevent a possible allergic reaction to the T cell
administration. If after the second infusion there is a reduction in the size of the
patient's lymphoma on CT or MRI scan as assessed by a radiologist, the patient can receive up
to six (6) additional doses of the T cells at monthly intervals if they wish. All of the
treatments will be given by the Center for Cell and Gene Therapy at Houston Methodist
Hospital or Texas Children's Hospital.
In between the first and second T cell infusions and for 6 weeks after the last infusion, the
patient should not receive any other anti-cancer treatments such as radiation therapy or
chemotherapy. If the patient does receive any other therapies in-between the first and second
infusion of T cells, they will be taken off treatment and will not be able to receive the
second infusion of T cells.
MEDICAL TESTS BEFORE TREATMENT
- Physical exam.
- Blood tests to measure blood cells, kidney and liver function.
- Measurements of your tumor by routine imaging studies. We will use the imaging study
that was used before to follow your tumor: CT, MRI, or PET.
- Pregnancy test if you are a female who can have children.
MEDICAL TESTS AFTER TREATMENT
- Imaging study 6 weeks after the 2nd TAA-CTL infusion.
To learn more about the way the T cells are working in the patient's body, an extra 20-40 mL
(4-8 teaspoons) of blood will be taken before each cycle of aza (if applicable), 2 weeks
after each cycle of aza (if applicable), before each T-cell infusion, and at Weeks 1, 2, 4
and 6. One additional blood sample might be drawn 3 to 4 days post the T-cell infusion; this
is optional. Afterwards, blood will be collected at 3, 6, 9 and 12 months after the last
infusion. The blood may be drawn from a central line at the time of the patient's regular
blood tests. Investigators will use this blood to see how long the T cells last,and to look
at the immune response to the patient's cancer.
Study Duration: Patients will be on active study participation for approximately one year.
Patients who receive additional doses of the T cells as described above will be actively
followed until 1 year after their last dose of T cells. Investigators will then remain in
contact with patients once a year for up to 4 additional years (total of 5 years follow-up)
in order to evaluate disease response long-term.
Other known NCT identifiers