(Participants 19 – 70)
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 multidisciplinary organization.
This research project is funded by the Canadian Institutes for Health Research, Health Canada,
and by Genzyme Corporation, Cambridge, MA.
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
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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.
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
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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 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
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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.
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
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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 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
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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}
Site PI}
{Enter telephone number of
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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