Allogeneic CTL Study
Recipient Treatment Consent
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August 15, 2008
CONSENT FORM
RECIPIENT CONSENT
Most-closely HLA Matched Allogeneic Virus Specific Cytotoxic T-Lymphocytes
(CTL) to Treat Persistent Reactivation or Infection with Adenovirus, CMV and EBV
after Hemopoietic Stem Cell Transplantation
Background
In this consent "you" refers to you or your child.
You have a type of blood cell cancer, other blood disease or a genetic disease
for which you have received a stem cell transplant. After transplant while the
immune system grows back you are at risk of infection and you have had an
infection with one or more of three viruses - Epstein Barr virus (EBV),
cytomegalovirus (CMV) or adenovirus – that has persisted or recurred despite
standard therapy.
Adenovirus is a virus that just causes symptoms of a common cold normally but
which can cause serious life-threatening infections in patients who have weak
immune systems. It usually affects the lungs and can cause a very serious
pneumonia, but it can gut the liver, the pancreas and the eyes.
CMV is a virus that can also cause serious infections in patients with suppressed
immune systems. It usually affects the lungs and can cause a very serious
pneumonia, but it can also affect the intestinal tract, the liver and the eyes.
Approximately two-thirds (2/3) of normal people harbor this virus in their body. In
healthy people CMV rarely causes any problems because the immune system
can keep it under control. If you and/or your donor are positive for CMV, you are
at risk of developing CMV disease while your immune system is weak post
transplant.
EBV is the virus that causes glandular fever or kissing disease. It is also normally
controlled by a healthy immune system but when the immune system is weak
can cause fevers, enlarged lymph nodes and some times develop into a type of
cancer called lymphoma.
We are therefore asking if you would like to participate in this study which tests if
blood cells from a donor that is a partial match with you and your transplant
donor and that have been grown in a special way, can help treat infections with
these viruses.
This treatment with specially trained T cells (called CTLs) has had activity against
these viruses when the cells are made from the transplant donor. However as it
takes two to three (2-3) months to make the cells, that approach is not practical
when you already have an infection. We want to find out if we can use CTLs that
we have already made from another donor who matches as closely as possible
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and if they will last in your body and have activity against these viruses. These
cells are called “trivirus specific CTLs” because they can attack all three (3)
viruses.
Purpose
The purpose of this study is to find if trivirus specific CTLs from a donor who
matches you as closely as possible can help to treat your viral infection and how
long they last in your body.
Procedures
You will be one of approximately 45 subjects to be asked to participate in this
trial. The research will be conducted at the following location(s): Baylor College
of Medicine, TCH: Texas Children's Hospital, TMH: The Methodist Hospital; MD
Anderson Cancer Center, Duke University, Children’s Hospital of Los Angeles,
Massachusetts General Hospital and Dana Farber Cancer Center. If you wish to
consider this study your doctor will first look in a database to see if there is a CTL
line that is a close match with you and your donor using your HLA type which
measures six (6) proteins on the surface of your cells.
These CTL lines have been made at Baylor College of Medicine from donors for
other transplant patients or other normal donors from the National Marrow Donor
Program. All donors have been screened in the same way that we screen blood
donors. When the CTL lines were made blood was taken from the donors and
used to grow T cells. To do this we first infected blood cells called monocytes
with a specially produced adenovirus gene that also carries part of the CMV
gene. These monocytes with these new genes then stimulate the T cells. This
stimulation will train the T cells to kill cells with this part of the CMV virus or with
adenovirus. We then grow these CTLs with more stimulation with EBV infected
cells (which we will make from donor blood by infecting them with EBV in the
laboratory). We will also put the adenovirus that carries the CMV gene into these
EBV infected cells so that they too have CMV and adenovirus proteins. These
EBV infected cells will be treated with radiation so they cannot grow. By this type
of culture, we grow out T cells that can see and attack cells infected with EBV,
adenovirus or CMV. Once we have made sufficient numbers of T cells, we will
test them to make sure they kill cells infected with these viruses and freeze them.
If there is a line that matches at some HLA proteins with you, it will be shipped to
your transplant center. It will then be thawed and injected into your intravenous
line over one to five (1-5) minutes after you received Benadryl and Tylenol. We
will monitor your levels of these three viruses in your blood and also take blood to
see how long the cells are lasting.
All participants on this study will get the same dose of cells. However if you have
a partial response of your viral infection your doctors may offer you up to 4 more
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doses at 2 weekly intervals.
You will continue to be followed by your transplant doctors after the injection. You
will either be seen in the clinic or you will be contacted by a research nurse to
follow up for this study every week for four six (6) weeks and three (3), six (6),
nine (9), and 12 months. You may have other visits for your standard care. You
will also have regular blood tests done to follow your counts and the viral
infection. To learn more about the way the T cells are working in your body, an
extra 20-40 mLs (four to eight (4-8) teaspoons) of blood will be taken before the
infusion and then at two (2) and four (4) weeks and three (3) months. Blood
should come from the central intravenous line, and should not require extra
needle sticks.
Any left over samples of tissue (blood) may be used to help research. The
specimens may be kept for a long time. These specimens and information about
your circumstances may be shared with other cancer researchers. Although
there will be a record identifying under what circumstances these specimens
were obtained, under all circumstances your identity will be kept confidential.
Because the monocytes (or dendritic cells) and EBV infected cells that were used
to train the donor's T cells had a gene put in them, we will need to follow you for
one (1) year. You will either be seen in the clinic or you will be contacted by a
research nurse. In the event of death, we will request permission to perform an
autopsy to learn more about the effects of the treatment on your disease.
You can see and get a copy of your research related health information. Your
research doctor may be able to provide you with part of your information while
the study is in progress and the rest of your information at the end of the study
Potential Risks
In our studies, similar types of T cells made from the transplant donor have been
given to over 100 patients to prevent EBV lymphoma after transplant and to 28
patients to prevent infection with all three (3) viruses. Other investigators have
also given these cells to over 100 patients. Cells from a most-closely matched
donor have been given to over 50 patients in several studies. Most patients had
no side effects. In some patients with large EBV tumors the cells have caused
inflammation leading to fever and flu-like symptoms as well as swelling at the
tumor site. This swelling could be potentially dangerous and even life threatening
depending on the site. There is a possibility that body organs like the liver or
kidney could be damaged if the cells cause inflammation.
There is also a possibility that these T cells might try to attack other parts of your
body and cause graft versus host disease (GVHD). GVHD occurs when cells
from your bone marrow donor (graft) recognizes that your body tissues (host) are
different from those of the donor. When this happens, cells in the graft may
attack the host's skin, liver and intestines. If you have bad GVHD after the
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transplant, you will not be able to get the T cells. If you have GVHD after the T
cells have been given, we will treat you with steroids and other medicines.
Sometimes though GVHD can be hard to treat and does not respond to
treatment. It can even cause death.
There is also a possibility that the cells may not last very long because they are
not completely matched and your immune system may be able to see they are
foreign and kill them.
In this study we are using adenovirus to put a gene into monocytes and EBV
infected cells that will be used in the laboratory to stimulate the T cells. As the T
cells will be grown for several weeks after contact with the monocytes and
several days after contact with the EBV infected cells we think it is very unlikely
that any adenovirus or monocytes or EBV infected cells will be injected with the T
cells. However, should you receive any adenovirus it may cause an inflammatory
reaction. There is one report of a patient who received a large dose of
adenovirus into a blood vessel leading to his liver who died. Another risk is that
the cell line that we have infected with EBV and used to stimulate the T cells or
the EBV virus will be injected with the T cells. We think this is very unlikely and
we will also test the T cells before we use them to reduce the likelihood that any
of your cells that we have infected with EBV will be injected with the T cells.
Possible side effects from drawing blood may include pain or bruising at the site
of the needle puncture. There is a very small risk of an infection at the site of the
needle puncture. Also, it is possible that a person may faint when blood is drawn.
Care will be taken to clean the site well and therefore decrease the risk of
infection.
Because of potential or unknown effects of the study on a fetus, if you are a
woman of child-bearing potential, you must have a negative serum pregnancy
test prior to entry into this study.
You have been informed that either you or your partner(s) must utilize one of the
more effective birth control methods during the study and for six months after the
study is concluded. These consist of total abstinence, oral contraceptives, an
intrauterine device, contraceptive implants under the skin or contraceptive
injections. If one of these methods cannot be used, contraceptive foam with a
condom is allowed. In addition, the male partner should use a condom.
Since this is a research study, there may be risks that are currently unknown. We
will watch you very carefully for any side effects. If there are bad side effects, we
will stop the treatment.
Potential Benefits
You have been told that the benefits of participating in this study may be: That
these cells have activity against your viral infection. Additionally, your
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participation may help the investigators find out if these cells can be used instead
of medications. However, you may receive no benefit from participating in this
study.
Alternatives
The following alternative procedures or treatments are available if you choose
not to participate in this study: You can receive standard therapy with
Ganciclovir, Foscarnet, or Cidofovir if you have a CMV infection, Rituximab if you
have EBV or Cidofovir if you have adenovirus. Additionally, the same alternatives
are available during participation in this research project.
Subject Costs and Payments
You will not be charged for the modified T cell injection or for any evaluations that
are being done solely as part of your participation in this research project. You
will be charged for any tests or treatments that are being done as standard care
for your bone marrow transplant or your viral infection. You will have an
opportunity to discuss any financial concerns with a financial counselor
There could be considerable time and effort spent to develop a potential
commercial product which is a significant commitment of resources on the part of
this institution. Therefore, this institution does not plan to pay royalties to you
should a commercial product be developed from your blood or tissue as a
consequence of this research
Subject Rights
Your signature on this consent form means that you have received the
information about this study and that you agree to be a part of the study.
You will be given a copy of this signed form to keep. You are not giving up any of
your rights by signing this form. Even after you have signed this form, you may
change your mind at any time. Please contact the study staff if you decide to stop
taking part in this study.
The investigator or sponsor may decide to stop you from taking part in this study
at any time. You could be removed from the study for reasons related only to you
(for example, if you move to another city, if you do not take your study
medication, or if you have a serious reaction to your study medication) or
because the entire study is stopped. The sponsor may stop the study at any time.
There may be unknown risks/discomforts involved. Study staff will update you in
a timely way on any new information that may affect your health, welfare, or
decision to stay in this study. If you are injured because of this study, you will
receive medical care that you or your insurance will have to pay for just like any
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other medical care. You will not be paid for the injury.
Your Health Information
We may be collecting health information that could be linked to you (protected
health information). This protected health information might have your name,
address, social security number or something else that identifies you attached to
it. Federal law wants us to get your permission to use your protected health
information for this study. Your signature on this form means that you give us
permission to use your protected health information for this research study.
If you decide to take part in the study, your protected health information will not
be given out except as allowed by law or as described in this form. Everyone
working with your protected health information will work to keep this information
private. The results of the data from the study may be published. However, you
will not be identified by name.
People who give medical care and ensure quality from the institutions where the
research is being done, the sponsor(s) listed in the sections above,
representatives of the sponsor, agents of the Food and Drug Administration, and
regulatory agencies such as the U.S. Department of Health and Human Services
will be allowed to look at sections of your medical and research records related to
this study. Because of the need for the investigator and study staff to release
information to these parties, complete privacy cannot be guaranteed.
The people listed above will be able to access your information for as long as
they need to, even after the study is completed.
If you decide to stop taking part in the study or if you are removed from the study,
you may decide that you no longer allow protected health information that
identifies you to be used in this research study. Contact the study staff to tell
them of this decision, and they will give you an address so that you can inform
the investigator in writing. The investigator will honor your decision unless not
being able to use your identifiable health information would affect the safety or
quality of the research study.
The investigator, and/or someone he/she appoints in his/her place will try to
answer all of your questions. If you have questions or concerns at any time, or if
you need to report an injury related to the research, you may speak with a
member of the study staff: (832)824-4670 during the day and after hours.
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Members of the Institutional Review Board for Baylor College of Medicine and
Affiliated Hospitals (IRB) can also answer your questions and concerns about
your rights as a research subject. The IRB office number is (713) 798-6970.
Your signature on this consent form attests to the fact that you (your child)
_______________________________ have (has), within limits imposed by age,
maturity, and psychological state, given your (his/her) assent (affirmative
agreement) to participate in this research project.
Signature of Recipient
Signature of Investigator
Date
Date
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