AML16
NATIONAL CANCER RESEARCH
INSTITUTE
ACUTE MYELOID LEUKAEMIA
AND HIGH RISK MDS TRIAL 16
PATIENT INFORMATION SHEET 1 & CONSENT FORM 1
INTENSIVE TREATMENT
Local contact details
NCRI AML16 TRIAL
AML16 Patient Information Sheet and Consent Form 1, Version 4 – May 2006
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PATIENT INFORMATION SHEET 1 & CONSENT FORM 1
1.
Study title
AML16 Trial
2.
An invitation to participate in the AML16 trial
You are being invited to take part in a research study. Before you decide it is
important for you to understand why the research is being done and what it will
involve. Please take time to read the following information carefully and
discuss it with others if you wish. Ask us if there is anything that is not clear or
if you would like more information. Take time to decide whether or not you
wish to take part.
Thank you for reading this information. If you decide to take part you will be
given a copy of this information sheet and your signed consent form
3.
What is the purpose of the AML16 trial?
Acute Myeloid Leukaemia (AML) and Myelodysplasia (MDS) are malignant
conditions of the bone marrow. They both result in failure of the bone marrow
to manufacture enough blood cells (red cells, white cells and platelets),
because the marrow contains too many leukaemia cells. The details of these
conditions will have been explained to you by your Haematology Team. There
are two approaches to treatment. The first is to use intensive chemotherapy
which comprises between 2 and 4 courses of intensive chemotherapy which
are given 4-6 weeks apart usually as an inpatient. The aim of this treatment is
to kill off the leukaemia cells and allow the marrow to work normally which is
called disease remission. Because there is a risk of the disease coming back
a further 2 or 3 courses of treatment are given. This approach has risks
associated with it which your team will have explained, and this approach may
or may not be considered suitable for you because of your age or for other
medical reasons.
The second approach, which is called a non-intensive approach, is to use
drugs to control the leukaemia cells in the bone marrow rather than to try to get
ride of them completely. This approach is less intensive and some of the
treatments can be given by mouth and taken as an outpatient. The chances of
the disease going into complete remission are lower, but much less time in
hospital is required. For some patients, particularly those who are less fit or
have other medical conditions, this may be thought to be a better approach.
Which treatment approach is adopted for you will be decided after you have
had a discussion with your doctor.
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The AML 16 trial is a national study being undertaken in the UK. The aim is to
compare new treatments for both of the approaches discussed above with
what could be regarded as standard treatments.
Patients Eligible for Intensive Treatment
For patients for whom an intensive approach is though to be suitable, standard
treatment which is a combination of two drugs called Daunorubicin and
Cytarabine will be compared with Daunorubicin and a new drug called
Clofarabine for the first two courses of treatment. In addition the trial will
examine the value of adding another new drug called Mylotarg to these
treatments in the first course. This means that patients who enter this part of
the trial will receive one of four treatment options:
-
Daunorubicin + Cytarabine
or
Daunorubicin + Clofarabine
or
Daunorubicin + Cytarabine + Mylotarg
or
Daunorubicin + Clofarabine + Mylotarg.
Patients will be allocated to a treatment by a process called “randomisation”.
This means that a computer programme will be used to give you an equal
chance of getting one of the four treatment options. In course 2 the same drug
combination will be used but Mylotarg will not be given.
The trial will also try to find out whether a total of 3 courses of treatment are
better than 2 courses, and whether low dose maintenance for 12 months is
beneficial. This will be explained in a separate information and consent form.
Patients Eligible for Non Intensive Treatment.
Our Group’s previous trial for patients who were treated with a non-intensive
approach showed that low doses of Cytarabine were better than tablets called
Hydroxyurea. Both could be given on an outpatient basis. However there is
much room for improvement. In the AML16 trial we intend to assess 4 new
drugs either alone or in combination, all of which have had preliminary
evaluation and shown activity. These drugs are called Mylotarg, Clofarabine (in
lower dose than being used in the intensive treatment), Zarnestra and
Trisenox. Patients who enter this part of the trial will receive one of five
treatment options, either Low Dose Cytarabine or Low Dose Clofarabine or
Low Dose Cytarabine + Mylotarg or Low Dose Cytarabine + Zarnestra or Low
Dose Ara-C + Trisenox. The aim is to find out if any of the 4 new options is
better than Low Dose Cytarabine alone. Each treatment will be given for 4
courses around 4 to 6 weeks apart.
-
Low Dose Cytarabine
or
Low Dose Clofarabine
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-
or
Low Dose Cytarabine + Mylotarg
or
Low Dose Cytarabine+ Zarnestra.
Or
Low Dose Cytarabine + Trisenox
Patients will be allocated to a treatment by a process called “randomisation”.
This means that a computer programme will be used to give you an equal
chance of getting one of the four treatment options.
In addition to the treatment part of this trial you will be asked to consent to
donating any excess material that is left over from the diagnostic tests for
research. You will receive an information sheet and consent form for this, but
you do not have to agree to this to take part in the main trial.
4.
Why am I being invited to take part in the AML16 trial?
Your doctor has diagnosed AML or MDS which requires to be treated with
chemotherapy. This research study is aimed at testing new combinations of
drugs – each of which has already been given to patients separately – in the
hope that by combining them together the treatment will be better.
5.
Do I have to take part in the AML16 trial?
No. It is up to you to decide whether or not you want to take part. If you decide
to take part you will be given this information sheet to keep and you will be
asked to sign a consent form. You will be given an information sheet and
consent form at each point in the trial where there is a treatment decision to be
made. Even after deciding to take part you are still free to withdraw from the
trial at any time and without giving a reason. A decision to withdraw at any
time, or a decision not to take part, will not affect the standard of care you
receive.
6.
What will happen to me if I take part in the AML16 trial?
The first thing that will happen is that you and your doctor will decide whether
your treatment approach will be with intensive or non-intensive treatment. If it
is decided that you will have one of the non-intensive treatment options you
will be provided with a separate patient information and consent form.
If you have decided to be treated with intensive chemotherapy please read the
rest of this information and consent form. If you think that you would prefer to
take part in the non-intensive treatment, please ask for the other information
and consent form.
The Trial will be comparing new approaches for the first two course of
treatment. Patients in the AML16 Trial who are allocated to intensive treatment
will receive either a 10 day course of intravenous therapy (Daunorubicin and
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Cytarabine) with or without the new drug called Mylotarg given as a single
infusion on day 1 of treatment, or a 5 day course of treatment using
Daunorubicin together with a new drug called Clofarabine, with or without
Mylotarg on day 1. All drugs are given by a drip over 1 or 2 hours. You will be
given sickness medication to reduce the chance of nausea or vomiting. After a
break of 4 or 5 weeks you will receive a second course of the same treatment
but without Mylotarg. These treatments will be given to you as an inpatient.
After the treatment is finished you may be allowed to be at home with close
outpatient follow-up.
Treatment
Allocation
Course 1
Course 2
Dauno Ara-C
or
Dauno Clofarabine
Dauno +Ara-C
or
Dauno Ara-C
with Mylotarg
or
Dauno Clofarabine
with Mylotarg
Dauno+Clofarabine
Dauno + Ara-C
Dauno + Clofarabine
Once this part of treatment has been completed and an assessment of
response has been made by re-examining your bone marrow, you may be
allocated treatment with a third course of treatment with or without
maintenance therapy, but this will be explained in a separate information and
consent form which will be given to you nearer the time.
During and after treatment your medical team will monitor your condition,
which will involve regular blood tests and occasional bone marrow
examinations, but this is normal care.
After each treatment course is complete your treatment team may be happy
for you to go home. They will give you information about what to do and what
not to do, which will include advice on diet. You will be seen regularly for
assessment of your progress during which any side effects that you are
experiencing will be noted. Routine blood tests will be done to check that your
blood counts and blood chemistry is reacting as expected. This is all normal
follow-up practice. After 3 or 4 weeks there may be evidence that your blood
counts are returning to normal. Your doctor will want to assess the response
by examining your bone marrow. If he/she considers that you are improving,
he/she will arrange for the second course of treatment to be given to you. You
will have the same follow-up monitoring after course 2.
7.
What does taking part in the AML16 trial involve?
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The treatment allocated to you will be decided by a process of randomisation.
By this process, which will be carried out by a computer programme, patients
are allocated treatment by All chemotherapy suppresses the normal immune
system and the infection fighting white blood cells as well as the leukaemia
cells. As a result, there is an increased risk of infection for patients with AML.
While at home, you should avoid contact with people who have got infections
like the cold or chest infections in case you pick up the infections. The nurses
on the ward will tell you, or the person who looks after you at home, how to
take your temperature. You will need to come back to hospital quickly if you
get an infection.
Your treatment team will give you advice about what food to eat and what to
avoid. You may not feel like driving after chemotherapy and it is better for you
not to try. It would be helpful if someone can bring you to hospital in a car so
you do not have to travel on public transport. If this is not possible, the
hospital should be able to arrange some suitable transport for you.
Your ward nurse or Clinical Nurse Specialist (CNS) will be able to tell you more
about this and some of the other effects of chemotherapy.
8.
What is the treatment being tested in the AML16 trial?
The first part of the trial is comparing the standard drug, Cytarabine, with a
new drug called Clofarabine, each in combination with a standard drug called
Daunorubicin. In addition the trial will test the value of adding a drug called
Mylotarg on day 1 of the first course of treatment. As well as finding out
whether the combination is better at controlling leukaemia, we will also be
monitoring your condition to make sure that the side effects are acceptable,
and not more than we would normally expect.
9.
What are the alternatives for treatment of older patients with AML
or high risk MDS?
There are two main ways of treating AML in older patients. The first of these is
with intravenous chemotherapy, similar to what you might have in this study.
The idea of this approach is to eliminate the leukaemia. The alternative is to
use less intensive chemotherapy which has a lower chance of getting rid of the
leukaemia, but would not require you to be in hospital so frequently. Usually
this latter approach is reserved for patients who may not tolerate, or who do
not want, the more intensive treatment. Your doctor will have discussed these
options with you. Standard treatment, which you are likely to receive if you do
not enter this trial, is 3 or 4 courses of chemotherapy using a combination of
drugs (for example Daunorubicin and Cytarabine). Each course would last
between 5 to 10 days and would be given in hospital, with breaks of 4 to 5
weeks between courses.
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10.
What are the side effects of the treatment received when taking
part in the AML16 trial?
The most common side effects of chemotherapy drugs affect three main types
of cells in the body: the lining of the bowel, the skin and hair and the bone
marrow.
All chemotherapy drugs, including those in this study, can cause nausea and
vomiting but you will be given other drugs to prevent this becoming a problem.
Other side effects include constipation and diarrhoea and soreness in the
mouth. You will be asked to use mouth wash regularly to help with this.
Hair loss occurs with all intravenous chemotherapy drugs used for AML.
However, the hair always grows back a few months after the treatment is
completed. Clofarabine, which is part of this study, sometimes causes a rash,
particularly on the hands and feet. This also goes away when treatment is
finished, but may need treatment with steroid medicines. Very occasionally
people can feel sleepy when receiving Clofarabine, but this is very unusual
except at doses higher than you would get in this trial.
The normal bone marrow cells, as well as the leukaemia cells, will be
damaged by the chemotherapy. This will result in lower than normal white
blood cells (which prevent infections), platelets (which help to clot the blood)
and red blood cells or haemoglobin (which is the red part of blood which
carries oxygen). You will need blood or platelet transfusions to help with low
blood counts and you will be given antibiotics to help prevent infections when
your white blood cells are low. If you get an infection, you will need to come
back to hospital to get intravenous antibiotics. These effects will occur with
any effective chemotherapy.
Part of the new drug in this study (Mylotarg) is an antibody. Sometimes people
can have temperatures or shaking when antibody treatments are given. This
is usually very temporary and is largely prevented by giving a small dose of
steroids about an hour before the Mylotarg.
Both Clofarabine and Mylotarg can also cause upset in some blood tests of the
liver function. This usually happens around 7 days after the treatment and you
will usually not notice anything. Very occasionally, more serious liver
abnormalities can happen causing jaundice. If this happens, you will probably
need to come back into hospital for observation or treatment. Usually the
jaundice settles after a few days of treatment.
Although Clofarabine and Mylotarg have been used in many patients across
the world, they are still quite new treatments and there may be other side
effects which we do not know about yet. Please discuss any unusual
symptoms with your doctor.
11.
What are the possible disadvantages and risks of taking part in the
AML16 trial?
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If you have private health insurance cover, you should discuss this study with
the insurance company to check that it will not affect your insurance.
Any treatment with intensive chemotherapy damages the immune system.
Therefore, there is an increased risk of infection for people with leukaemia.
However, it is not thought that the treatment being offered in this trial will worse
compared to other sorts of intensive AML treatment.
All patients will have the same number of blood tests during the first part of the
study as they would have with any treatment of AML.
Chemotherapy also damages sperm and may cause damage to unborn
babies. Men receiving chemotherapy should use effective contraception if
engaging in sex. Women who may still be able to become pregnant should
also use contraception and your doctor will be able to arrange a pregnancy
test if you think this is a possibility.
12.
What are the possible benefits of taking part in the AML16 trial?
We hope that all the possible treatments in this study will help you, but this
cannot be guaranteed. However, the information we get from this study may
help us to better treat future patients with AML.
13.
What if new information becomes available during the course of
the AML16 trial?
Sometimes during the course of a trial, new information becomes available
about the treatment that is being studied. If this happens, your doctor will tell
you about it and discuss with you whether you want to continue in the study. If
you decide to withdraw from the study, your doctor will make arrangements for
your care to continue. If you decide to continue in the study you may be asked
to sign an updated consent form.
Also, on receiving new information your doctor might consider it to be in your
best interests to withdraw you from the study. Your doctor will explain the
reasons and arrange for your care to continue.
14.
What happens when the AML16 trial stops?
Very occasionally a trial is stopped earlier than anticipated. This is very
unusual, but, if this happens, the reasons will be explained to you and your
doctor will make arrangements for your treatment to continue.
15.
What if something goes wrong?
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If you are harmed by taking part in this research project, or if you are harmed
due to someone’s negligence, then you may have grounds for a legal action.
Regardless of this, if you wish to complain, or have any concerns about any
aspect of the way you have been approached or treated during the course of
this study, the normal National Health Service complaints mechanisms are
available to you.
16.
Will my taking part in the AML16 trial be kept confidential?
All information collected in the AML16 trial will remain strictly confidential in the
same was as your other medical records. If you agree to take part, your doctor
will send information about you, your condition and your progress to the trial
data collection centre at the University of Birmingham Clinical Trials Unit
(BCTU). This information will be put into a computer and analysed by the AML
trial office staff. All information will be held securely and in strict confidence.
Named information about you will be passed to the Office of National Statistics
(ONS) which is part of the General Register Office (GRO) in order to follow
your health status. All personal details will be treated as strictly confidential by
these organisations. Also if you consent to take part in the research, your
medical records may be inspected by the hospital personnel or the Chief
Investigator or his nominee for the purpose of analysing the results. on behalf
of the NCRI. The NCRI is the UK’s organisation which ensures studies like this
one are appropriate. Your notes may also be looked at by people from
regulatory authorities to check that the study is being carried out correctly.
Your GP will be informed of your participation in the trial. There is a space on
the consent form for you to confirm that you are aware of this.
17.
What will happen to the results of the research study?
When the AML16 trial is completed, the results will be published in a medical
journal so other doctors can see the results. You can ask your doctor for a
copy of any publication. If published, your identity and personal details will be
kept confidential. No named information about you will be published in any
AML16 trial report.
18.
Who is organising and funding the research?
The study is organised by the NCRI AML Working Party which has many years
of experience in running trials in Leukaemia. Your doctor is not receiving any
money or other payment for asking you to be part of the study.
The overall responsibility for ensuring the proper conduct of the trial belongs to
Cardiff University. The AML16 trial, data collection and analysis, and
administration will be provided by BCTU.
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19.
Who has reviewed the AML16 trial?
The study has been internationally scientifically reviewed and approved by a
national committee representing the Medical Research Council, Cancer
Research UK and the Leukaemia Research Fund.
It has received
authorisation from the Medicines and Healthcare Products Regulatory Agency
(MHRA) and National and Local Ethics Committee and the participating
hospitals’ Research and Development Office.
20.
Contact for Further Information
Further information can be obtained from your local organiser (Principal
Investigator) or the UK organiser (Chief Investigator) whose addresses are
given below.
Chief Investigator:
Prof Alan Burnett
Department of Haematology
University Hospital of Wales
Cardiff
CF14 4XW
Tel: 029 2074 2375
e-mail: BurnettAK@cardiff.ac.uk
Thank you for taking the time to consider taking part in this study.
AML16 Patient Information Sheet and Consent Form 1, Version 4 – May 2006
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Page 10 of
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NATIONAL CANCER RESEARCH INSTITUTE
ACUTE MYELOID LEUKAEMIA AND HIGH RISK MDS TRIAL 16
CONSENT FORM 1
Name of Researcher:
Insert local researchers name
Chief Investigator: Professor Alan K Burnett
Please initial box
1. I confirm that I have read and understand the information sheet (Version
4, May 2006) for the above study and have had the opportunity to ask
questions.
2. I hope to complete the study, but I understand that my participation is
voluntary and that I am free to withdraw at any time, without giving a
reason, and without my medical care or legal rights being affected.
3. I understand that my doctor will provide information about my
progress, in confidence, to the Trial Data Centre at BCTU. I
understand that the information held by the NHS and records
maintained by the Office of National Statistics may be used to keep in
touch with me and follow up my health status.
4 I understand that the information will be used for medical research
only and that I will not be identified in any way in the analysis and
reporting of the results. I understand that sections of any of my
medical notes may be looked at by responsible individuals from the
NCRI AML Working Group or from regulatory authorities where it is
relevant to my taking part in this research. I give permission for these
individuals to have access to my records.
5. I am aware that GP will be informed of my participation in this study.

6 I agree to take part in the above study.

________________________
Name of Patient
______________
Date
____________________
Signature
_________________________ _____________
Name of Person taking consent Date
(if different from researcher)
____________________
Signature
_________________________
Researcher
____________________
Signature
______________
Date
1 for patient; 1 for researcher; 1 to be kept with hospital notes; 1 copy to
BCTU
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