(Participants 16 – 18)
Information/Consent Form (Participant)
PROJECT TITLE
A Randomized Trial of Thymoglobulin to Prevent Chronic Graft versus Host Disease in Patients
Undergoing Hematopoietic Progenitor Cell Transplantation from Unrelated Donors.
PRINCIPAL INVESTIGATOR FOR CANADA
Dr Irwin Walker, MBBS, FRCP(C), FRACP, McMaster University and Hamilton Health Sciences, Ontario,
Canada.
SPONSOR and FUNDING
The sponsor is McMaster University, Faculty of Health Sciences. Administrative support is provided by
the Canadian Blood and Marrow Transplant Group (CBMTG), a non-profit multi-disciplinary organization.
This research project is funded by the Canadian Institutes for Health Research, Health Canada, and by
Genzyme Corporation, Cambridge, MA.
WHO SHOULD READ THIS CONSENT FORM?
The information in this consent form is intended for the participant (the person who is being invited to
participate in this research project) and the parent(s) or guardian(s) of the participant.
THE REASON FOR THIS RESEARCH PROJECT
We are trying to decrease the likelihood and severity of graft versus host disease. You are being invited
to participate in this research project because you are having either a bone marrow or blood progenitor
cell transplant from an unrelated donor and because graft versus host disease is a frequent and
sometimes serious complication of this procedure. Your participation in this study is entirely voluntary
and choosing not to take part will not affect your decision to have the transplant or the standard of
medical care which you will receive.
The project is testing whether giving a medication known as Thymoglobulin will decrease the frequency
and severity of graft-versus-host disease (GVHD), a common and serious side effect of transplantation.
In order to decide whether or not you want to be a part of this research study, you should understand
what is involved and the potential risks and benefits. This form gives detailed information about the
research study, which will be discussed with you. Once you understand the study, you will be asked to
sign this form if you wish to participate. Please take your time to make your decision. Feel free to
discuss it with your friends and family and/or your family physician.
You will be receiving a bone marrow or blood progenitor cell transplant from a donor who is not related
to you. GVHD is more likely to occur than if you had had a donor who was related to you. The likelihood
that GVHD will occur is about 80%. As well, GVHD is also more likely to be severe when the donor is
unrelated. This means it (GVHD) is more likely to be life-threatening or to seriously affect your long
term health even if the underlying cancer is cured. GVHD is the most common reason that transplants
fail when unrelated donors are used, which is why we are testing Thymoglobulin.
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Graft-versus-host disease (GVHD) is a reaction of the donor’s immune system against the recipient’s
(your) tissues. When GVHD is mild and directed mainly against the cancer it is a benefit because it
decreases the likelihood that the cancer will relapse. However, if it reacts against your normal tissues it
may be harmful, even life threatening. The harm from it usually outweighs its benefit. We would want
you to have a mild degree of GVHD for the benefit, but we want to prevent it being severe.
When GVHD starts within three months after transplantation it is called acute GVHD. Acute GVHD
causes skin rashes, inflammation of the liver and gastrointestinal side effects such as nausea, diarrhea
and ulcers. When GVHD continues or starts after three months it is called chronic GVHD. Chronic GVHD
commonly affects the skin and soft tissues, can interfere with movement, causes soreness of the mouth
that can interfere with eating, and can cause dryness and soreness of the eyes. Chronic GVHD can also
affect many other parts of the body, including the lungs. Chronic GVHD is less likely than acute GVHD to
be life-threatening but it causes ill health that can last for a number of years. Both acute and chronic
forms of GVHD cause delays in recovery of the immune system making you at risk of infections that
themselves can be dangerous.
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY
About 198 patients from Canada (mainly), and possibly other countries, will take part in this study. It
will take about 3.5 years to enroll all the patients. Patients will be followed by the transplant team for 2
years after the transplant for this research, but for your health as long and as often as recommended.
WHAT IS THYMOGLOBULIN?
Thymoglobulin is a concentrated solution of antibodies made from the serum of rabbits after they have
been injected with the human immune cells that cause GVHD. The rabbits react to the human immune
cells by producing these antibodies. These antibodies are refined into the product known as
Thymoglobulin® that can then be used to reduce the number of donor immune cells that cause GVHD.
Thymoglobulin is a medication that is given by vein (intravenous). It has been tested in Europe and is
licensed for use in bone marrow transplantation to prevent GVHD. In North America, Thymoglobulin is
licensed for use only in kidney transplantation. We would like to test its use in patients who are having
allogeneic bone marrow or blood progenitor cell transplants in Canada, so as to confirm the beneficial
results in the European studies and establish its use here in North America.
WHAT ARE THE POSSIBLE RISKS AND DISCOMFORTS?
The risks are having side effects of Thymoglobulin. Side effects from Thymoglobulin are quite common,
but are nearly always temporary and settle with medication or once the infusion is over. About 60% of
people will have a mild fever during the intravenous infusion, about 30% will have shivering or a skin
rash. Occasional patients (5-10%) may have a drop in blood pressure. If such reactions are severe, the
infusion may be stopped for a time until the symptoms clear. Benadryl, acetaminophen (e.g. Tylenol)
and steroids are given before the infusion to minimize these reactions and may be repeated during the
infusion. When reactions occur they are most likely to be troublesome only on the first day. It is most
unlikely that side effects would be severe enough to discontinue Thymoglobulin altogether.
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Another (possible and theoretical) side effect of Thymoglobulin could be to increase the chance that you
may develop a serious infection, but when tested in Europe this wasn’t so. You will be monitored
closely for such infections.
A potentially very serious side effect is infection with a special virus called EB virus that can lead to
lymph gland cancer (Post Transplant Lymphoproliferative Disorder). This has been reported on rare
occasions following bone marrow transplantation and is more common when Thymoglobulin is used. It
appears to be uncommon, occurring in approximately 3% of transplant recipients. Your blood will be
tested once a week for EB virus infection. Treatment is often very effective when given soon after
infection is detected.
WHAT ARE THE POSSIBLE BENEFITS FOR ME OF AGREEING TO TAKING PART IN THIS STUDY?
The possible benefit to me would be preventing a serious case of graft versus host disease that could
threaten my health or life.
WHAT ARE YOU CONSENTING TO?
If you agree to take part in this research project you will be taking part in a randomized trial. Before the
transplant you would be assigned by a computer, by randomized chance like the toss of a coin, to either
receive Thymoglobulin in addition to the normal transplant procedures, or receive the transplant
without Thymoglobulin and be part of a matching group. The chances are 50% that you will be either in
the Thymoglobulin-receiving group or the matching group. We will then compare the results of the two
groups. If you decline to take part in this research project the transplant procedure will be carried out in
exactly the same way but without Thymoglobulin being given.
If you agree (consent) to take part in this research project, the only procedure that will be different from
the normal transplant procedures, and the only research procedures that you will be consenting to will
be the infusion of Thymoglobulin and the filling out of some questionnaires so that we can better
understand how you are feeling. The Thymoglobulin administration and questionnaires are described as
follows:
The date and schedule of other procedures for the transplant will not be changed in any way than if you
were not taking part in this project. Thymoglobulin is given by intravenous injection over a number of
hours, each day for three days, on the day of transplant and on the two previous days. The dose on the
first day is one quarter of the dose on the other two days, the dose being 0.5 mg for each kilogram of
your body weight on the first day, and 2.0 mg per kilogram on each of the next two days. After
discharge there will be no additional medications or procedures and you will not have to attend the
clinic any more often than if you had not taken part in the project. We will, though, ask you to fill in
some questionnaires, as follows:
After the transplant we will be interested in your opinion and feelings about how the transplant has
affected you. We will ask you to fill out some questionnaires (Quality of Life questionnaires) before the
transplant and then at six, twelve and 24 months following transplant. These questionnaires take
approximately 20-30 minutes to complete. Some of the questions are personal; you can refuse to
answer these questions if you wish. The information you provide is for research purposes only and will
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remain strictly confidential. The individuals (e.g. doctors, nurses, etc) directly involved in your care will
not usually see your responses to these questions – if you wish them to know this information, please
bring it to their attention.
A research nurse or research assistant who works at this transplant centre will administer the
questionnaires. This person will explain how to complete the questionnaires. If the questionnaires are
being completed by interview, it is this person who will be asking the questions. The person who
administers the questionnaires will check your completed questionnaires to ensure you’ve understood
the directions correctly. They are only looking for questions that you may have missed by accident or
items you may have misunderstood. They will not discuss the answers you have given in detail. (If there
are questions you have left blank on purpose, please communicate this to the person administering the
questionnaire.)
Although your individual answers will not be shared with the transplant centre team and will not be filed
in your medical chart (unless you request this), your study doctor and the study nurse may be notified of
the overall “score” (result) of one of the questionnaires (depending on your score). This questionnaire
is called the “CES-D Scale”. The purpose of this questionnaire is to assess your level of emotional
distress. Once you complete this questionnaire it will be sent to the Project Management Office. The
score of your CES-D questionnaire will be calculated. If your score indicates a high level of emotional
distress the Project Management Office will then notify {enter name of site PI and study coordinator}.
{Enter name of site PI and study coordinator} will contact you regarding a referral to a psychologist,
social worker or your family doctor. You do not have to accept this referral if you don’t wish to.
Previous studies in which the CES-D scale has been used have shown that a referral to a mental health
professional can be beneficial when a score indicates a high level of emotional distress. That is why this
process is being followed. (This process is not being followed for the other questionnaires.)
The researchers would also like to collect information about your bone marrow transplant and follow-up
to compare costs related to the two different transplant procedures in this study. The researchers are
requesting your permission to access your medical chart(s) and data bases (that already exist for
auditing and accounting purposes) in order to obtain health economic information. By signing this
consent you agree that the researchers can access this information for the purposes of this study.
CONTRACEPTION AND PREGNANCY:
The effects of Thymoglobulin on the unborn child are unknown. The effects of chemotherapy (and
other medications you may receive before and after transplant) are not well known. Therefore, women
who are pregnant or breastfeeding cannot be enrolled in this study.
Women of childbearing potential who are enrolled in the study must agree to use an adequate method
of birth control from the time of enrollment until a minimum of one year following transplant.
Men enrolled in this study must agree to use an adequate method of birth control from the time of
enrollment until a minimum of one year following transplant.
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It is important that you discuss the implications of discontinuing birth control after one year post
transplant with your transplant doctor. In some cases it may be recommended that pregnancy (or
fathering a child) should be prevented for a longer time period.
Adequate methods of birth control include:
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Abstinence
Previous tubal ligation
Vasectomy
Oral, injectable or implantable contraceptives
Condoms
Foam
IUD
If you become pregnant (or father a child) at any time from your enrollment in this study until 2 years
following your transplant (the end of the study follow-up period), then you should inform your
transplant doctor and the study doctor immediately. You will be asked for your permission regarding
access to the health records of your pregnancy (if you are female) as well as the health records of your
infant.
IF I DO NOT WANT TO TAKE PART IN THE STUDY, ARE THERE OTHER CHOICES?
If you do not want to take part in this study it will not affect the decision to have the transplant.
Choosing not to participate in this study will in no way affect your care or treatment.
DECLARATION OF FINANCIAL INTEREST
Neither the Investigator nor the institution has a financial interest or a proprietary interest in the drug,
procedure or device under study.
RESEARCH-RELATED INJURY
If you become ill or injured as a direct result of participating in this study, necessary medical treatment
will be available at no additional cost to you.
Your signature on this form only indicates that you have understood to your satisfaction the information
regarding your participation in the study and agree to participate as a subject. In no way does this waive
your legal rights nor release the investigator, the research doctor, the study sponsor or involved
institutions from their legal and professional responsibilities.
WITHDRAWAL FROM THE STUDY
If you choose to participate and later decide to change your mind, you can say no and stop the research
at any time. A decision to withdraw from the study will not affect your health care. Your physician or the
study sponsor may stop your participation at any time, without your consent, if they feel it is in your
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best interest. You may be taken out of the study, if you do not follow your doctor’s instructions, if you
experience a side effect that needs medical treatment, or if the sponsor stops the study for any reason.
COMPENSATION
No costs will be charged to you for being in this study, nor will you be paid for participating in the study.
You will not be charged for the research drugs or any research procedures.
CONFIDENTIALITY
You will not be identified as a study participant in any reports or publications of this research. Your
records will be kept in a locked file cabinet in a locked room. Only the staff involved in the research
study will see them. The research records will also be sent to the national study coordinator who is at
the Vancouver General Hospital, but your name will be removed beforehand.
With your permission, your family doctor will also be informed of your participation in this research
study. This consent form will be placed in your Health Chart.
It is unlikely, though possible, that records could be inspected by representatives from the Canadian
Institute of Health Research, the Health Canada agency that funded this research, or Genzyme who
funded part of this research, or the ethics committee at this hospital.
OTHER PERTINENT INFORMATION
Throughout the research study, you will be told about any new information that might affect your
decision about being in this research study. In particular, you will be told of any unforeseen risks that
may be identified.
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS?
You should ask questions about anything that you do not understand before you sign this form. The
study staff will also be available to answer questions before, during, and after the study.
If you have questions about taking part in this study, or suffer a research related injury, you can talk to
your doctor. You can also meet with the research nurse who discussed the project with you. You can
also meet with the doctor who is in charge of the study at this institution. That person is:
{Enter Name of Site PI}
{Enter telephone number of Site PI}
Or, you can speak with {Enter the name and telephone number for an independent research contact for
the institution}. You will receive a copy of this signed and dated consent form.
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CONSENT OF PARTICIPANT:
I have read the preceding information thoroughly. I have had an opportunity to ask questions and all of
my questions have been answered to my satisfaction. I agree to participate in this study. I understand
that I will receive a signed copy of this form.
Name
Signature
Date
Person obtaining consent (Investigator or Delegate):
I have discussed this study in detail with the participant. I believe the participant understands what is
involved in this study. In my judgment, this participant has the capacity to give consent, and has done
so voluntarily.
Name, Role in Study
Signature
Date
Signature
Date
Witness:
Name
This study has been reviewed by {Insert name of REB}. The REB is responsible for ensuring that
participants are informed of the risks associated with the research, and that participants are free to
decide if participation is right for them. If you have any questions about your rights as a research
participant, please call {Insert the contact information for the representative of the REB}.
It is possible the researchers may be interested in following your health status after the 2 year follow-up
period for this study. Do you agree to be contacted in the future regarding extended follow-up? If yes,
please initial _________.
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ASSENT OF PARTICIPANT:
I have had the opportunity to read this consent form, to ask questions about my participation in
this research, and to discuss my participation with my parent(s)/guardian(s). All my questions
have been answered. I understand that I may withdraw from this research at any time, and that
this will not interfere with the availability to me of other health care. I have received a copy of
the consent form. I assent (agree) to participate in this study.
Name
Signature
Date
PARENT / GUARDIAN:
I am satisfied that the information contained in this consent form was explained to my child /
ward to the extent that he/she is able to understand it, that all questions have been answered,
and that my child / ward assents to participate in this research.
Name
Signature
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Date
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