CORAL - Collaborative Trial in Relapsed Aggressive Lymphoma
Chemotherapy and Rituximab for Diffuse Large B-Cell Non-Hodgkin Lymphoma
Introduction
Diffuse large B-cell lymphoma is a type of Non Hodgkin’s lymphoma. In order to be eligible for this trial your
disease has to have come back after treatment or has continued to grow despite treatment. There are two standard
treatments recommended for someone in your position called DHAP and ICE. It is believed that the addition of the
drug rituximab to both of these treatments helps the chemotherapy be more efficient.
The drugs which make up R-DHAP are:
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Rituximab
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Dexamethesone
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Cistplatin
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Cytarabine
The drugs which make up R-ICE are:
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Rituximab
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Ifosphamide
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Carboplatin
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Etoposide
What is the aim of this trial?
This trial looks at two things. Firstly, the trial aims to compare two standard induction chemotherapy treatments
given to people whose disease has either continued growing during treatment or relapsed to see which is better at
getting the disease back into remission. The trial adds rituximab to both treatments as there is very good evidence
that this helps the chemotherapy become more efficient. Secondly, the trial looks at using rituximab as a
'maintenance' drug after a stem cell transplant to see whether this can reduce the chances of the disease returning.
Who can enter this trial?
You may be asked to enter this trial if you meet the following criteria:
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You are aged between 18 and 65
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You have a confirmed diagnosis diffuse large B-cell lymphoma which has continued growing during treatment or
relapsed
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You have been previously treated with chemotherapy combination containing anthracycline chemotherapy drugs with
or without rituximab (your doctor or nurse can tell you this)
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You are going to have a stem cell transplant
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You are well enough to undergo the treatment
What might stop me from entering this trial?
You won't be asked to enter this trial for the following reasons:
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You have a type of lymphoma called Burkitt's, mantle cell or T-cell lymphoma
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You have not been previously teated with chemotherapy combination containing anthracycline chemotherapy drugs
with or without rituximab (you doctor or nurse can tell you this)
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You have had a stem cell or bone marrow transplant in the past
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You have been treated with any trial drug in the 30 days before starting your first cycle of chemotherapy
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You have lymphoma in your brain or spinal cord
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If you have a serious medical condition
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If you are pregnant
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If you have had cancer in the last five years, apart from non-melanoma sking cancer or in situ carcinoma of
the cervix
Do I have to take part?
No. You are a key member of the health care team and it is completely up to you whether you want to be involved in
this trial. You have a right to say no or withdraw at any time without your ongoing care or treatment being affected.
If you do choose to take part you will be given lots of information and asked to sign a consent form.
How is this trial run?
This trial is known as a randomised control trial. A randomised control trial is a trial in which patients with
similar disease traits are selected by a computer to be placed in different groups that are comparing different
treatments. There is no way at the time for researchers to know which of the treatments is best and neither you
nor your doctor get to choose which treatment you have.
In this particular trial there are three parts; induction, consolidation and maintenance.
The Induction Phase
The first part of the trial is known as the induction phase. This is the phase where everyone in the trial
regardless of group receives one of the two standard induction chemotherapy combinations. In the induction
phase there are two main groups.
The first group
are given the R-ICE combination of chemotherapy. This is given through a central line drip over three
days at 3 weekly intervals. Each three weeks is called a cycle. During the first cycle you will receive two separate
doses of rituximab. On any further cycle you will only receive one. So, overall you will have 3 cycles of treatment
with 4 doses of rituximab.
The second group
are given the R-DHAP combination of chemotherapy. This is given through a central line drip over
three days at 3 weekly intervals. During the first cycle you will receive two separate doses of rituximab. On any
further cycle you will only receive one. So, overall you will have 3 cycles of treatment with 4 doses of rituximab.
At the end of the 2nd and/or 3rd cycle of chemotherapy you will be given a drug called G-CSF which increases the
number of stem cells in your blood. Your stem cells will then be collected and stored until you need them.
After the three cycles are complete regardless of whether you have received R-ICE or R-DHAP you will have a bone
marrow biopsy and a CT scan. This is to determine how well the treatment is working for you.
If these tests show that the treatment is not having an effect on your disease then you won’t continue onto the
second phase of the trial and your doctor will discuss other treatment options with you.
If the tests show that the treatment is working well for you and your lymphoma is in remission you will enter
part two known as the consolidation phase and be given a higher dose of chemotherapy and a stem cell transplant.
The Consolidation Phase
During the consolidation phase you will receive a different combination of chemotherapy known as BEAM. BEAM is
given at a higher dose than your previous chemotherapy combinations. BEAM refers to the following drugs;
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B = BCNU
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E = Etoposide
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A = Ara-C
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M = Melphalan
One week after your first dose of this combination of chemotherapy you will be given back your stem cells through
an infusion into your central line. This is painless and will look and feel like having a blood transfusion.
At this time you will be allocated to a group for the third part of the trial known as the maintenance phase.
The Maintenance Phase
Regardless of which group you were in for the induction phase you will be randomly allocated to one of the two
different groups in this phase.
If you are in the first group will not receive any further treatment but will be carefully monitored by the doctor.
Your doctor will physically examine you regularly and make a point of closely observing your condition.
If you are in the second group will be given further doses of rituximab. The doses of rituximab will start 28 days
after your stem cell transplant and continue once every eight weeks for approximately a year.
What might being entered in this trial mean to me?
Tests and hospital visits
Before you enter the trial you will have a number of tests. This will tell your health care team about your general
health and whether you are eligible for the trial or not.
The investigations may include:
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A CT scan
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Blood tests
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A bone marrow biopsy
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Physical examination
This trial will mean some overnight hospital stays for you. The number of nights depends on the phase of the trial
you are in.
In the induction phase you will have to stay overnight in hospital for two nights in order to have three days of
chemotherapy. This will happen during every cycle.
In the consolidation phase you may have to stay in hospital for about a month in order to receive your high dose
chemotherapy, the stem cell transplant and to give you lots of recovery time. You will see your doctor and have a
number of tests three months after the transplant.
In the maintenance phase you will come to the hospital as an outpatient every 8 weeks for about a year. During this
time you will receive your rituximab infusion.
Follow-Up
During the first year you will see your doctor every two months for a full physical examination and a number of
tests. For the second year this goes down to every six months and then you will see your doctor for an annual
follow up for five years.
Side effects
As with other treatments there are some side effects which you should know about. Your doctor or nurse can give
you much more detailed information on these effects and how you might manage them.