Download Help to inform an important clinical trial for patients with follicular

Help to inform an important clinical trial for patients with follicular lymphoma:
A request to patients with follicular lymphoma (or other forms of blood cancer)
Why we need your support
The improved understanding of the biology of blood cancer and the development of new technology
and more accurate diagnostic tests are enabling treatments to become more targeted with the
eventual aim of individualised treatment for every cancer patient.
The proposed PETReA clinical trial, outlined below, involves greater stratification of patients by
stepping up treatment for those with high-risk disease and scaling back treatment for patients with
low-risk disease. Reducing treatment has several important potential benefits including:
 Reducing side effects including serious infections
 Improving quality of life for patients
 Enabling savings of up to £50M a year in drug costs which could be used to help other cancer
patients
Understandably, however, some patients may be cautious about taking part in a clinical trial, where
their treatment may be reduced, because of a fear of relapse. For this reason, as part of the trial,
patients who decide to enter as well as those who decide not to take part will be interviewed to ask
for their views about the best ways to communicate and discuss this sensitive topic with patients.
Those patients who go on to take part will be monitored to see how long they stay in remission and
also how much psychological stress they experience/don’t experience.
The study has been developed through the National Cancer Research Institute (NCRI) Lymphoma
Clinical Studies Group (CSG) and has strong support from lymphoma doctors across the UK. An
outline application for funding was favourably reviewed by the Cancer Research UK Clinical Research
Committee and a full application has been invited. As part of this submission, the Committee has
requested more evidence that the trial would be acceptable to patients, taking into consideration
the possibility of low-risk patients not receiving a treatment which is currently approved by NICE as a
treatment option.
The Questions
The study team would be very grateful if you would read through the information on the following
two pages and answer these three questions.
1. Do you have follicular lymphoma?
YES/NO
2. Have you been diagnosed but are on ‘watch and wait’?
YES/NO
3. Would you be interested in taking part in this trial if you met the eligibility criteria?
DEFINITELY
PROBABLY
MAYBE
UNLIKELY
DEFINITELY NOT
4. What additional information or support would help you to make an informed decision about
taking part in this clinical study?
Thank you for your support.
1
The Clinical Study - a phase 3 evaluation of PET-guided, Response-Adapted therapy in patients
with previously untreated, high tumour burden follicular lymphoma (PETReA)
There are many different types of lymphoma but one of the most common forms is follicular
lymphoma (FL). FL is usually widespread at diagnosis but tends to grow slowly and have a good
prognosis. Treatment is indicated when the disease causes symptoms or complications. The first and least controversial - part of the treatment is called “induction”.
Induction treatment aims to shrink enlarged lymph nodes or other swellings and improve symptoms.
It consists of an antibody drug called rituximab (R) plus one of several different types of
chemotherapy. This drug combination is referred to as “R+chemo” and is very effective in most
patients. However, the disease eventually recurs, and patients go on to have second- and third-line
treatment, often with a different type of R+chemo.
“Maintenance” treatment consists of rituximab alone and is given after R+chemo induction. Several
trials have shown that R maintenance can prolong remissions after initial (frontline) or subsequent
induction treatment, and it is approved by NICE as a treatment option in both of these settings. On
the negative side, studies have also shown that R maintenance triples the risk of serious infection.
Most lymphoma doctors believe that the advantages of R maintenance after second- or third-line
induction treatment outweigh the disadvantages as it can prolong survival in this setting. In contrast,
R maintenance after frontline induction therapy does not prolong survival, possibly because patients
who don’t receive it here go on to receive it after second- or third-line induction where it may work
as well, if not better. Consequently, most lymphoma doctors regard R maintenance after frontline
R+chemo as controversial.
Careful analysis of the results of the main clinical trial investigating R maintenance after frontline
R+chemo (PRIMA) suggests that only 1 in 5 patients benefits from it, and that the benefit in these
patients consists of stopping the disease from growing back during the two years of drug treatment.
Ideally, R maintenance would be given only to the 1 in 5 patients who are likely to benefit from it,
sparing the rest from unnecessary side effects. However, until now we have not had a test that can
separate patients in this way.
PET (Positron Emission Tomography) is a new and very sensitive type of scan that detects many
types of cancer (including FL). It relies on the fact that cancer cells take up glucose (a sugar molecule)
more quickly than normal cells. Recently, three clinical studies have shown that PET scanning after
frontline induction treatment for FL is able to separate patients who relapse early (PET +ve, i.e.
disease still seen on the scan) from patients who are destined to have long-lasting remissions (PET ve, i.e. scan clear). The prognosis for patients who achieve PET negativity is excellent irrespective of
whether they receive R maintenance, with 50% still in remission and 95% alive at 6 years.
Interestingly, the proportion of patients with positive scan results (i.e. disease still visible) is about 1
in 5 – the same proportion who benefit from R maintenance. Our hypothesis is that these are the
same patients.
Based on these considerations, PETReA is asking two main questions:
1. Can R maintenance be omitted in the 4 in 5 patients who achieve PET negativity after frontline
R+chemo induction, thereby avoiding a 3-fold increase in the risk of serious infection (and
incidentally saving the NHS ~£50M per year in unnecessary drug costs)?
2
2. Can the outcome of the 1 in 5 patients who remain PET +ve after frontline R+chemo be
improved by stepping up the maintenance treatment? Here, we plan to investigate the benefit
of adding a drug called lenalidomide (or Revlimid) to R maintenance - the so-called R2 regimen.
Lenalidomide is a new drug that is taken by mouth and works in a completely different way to
chemotherapy or antibody drugs. Several clinical trials have shown that R2 is well tolerated and
highly effective in FL.
Patients entering the PETReA trial will have a baseline PET-CT scan followed by a 6-month course of
R+chemo (choice of 3 different types to suit individual patients) and then a second PET-CT scan. The
4 in 5 patients who become PET -ve at the end of the induction treatment will be randomly allocated
to receive 2 years of rituximab maintenance or no further treatment. Ordinary CT scans will be
performed at the end of this period and annually thereafter. The 1 in 5 patients who remain PET +ve
at the end of the induction treatment will be randomly allocated to receive 2 years of rituximab
maintenance or R2. A further PET-CT scan will be performed at the end of this period and ordinary CT
scans every year thereafter.
All patients will be followed up to see how long they stay in remission and how much psychological
stress they are experiencing. We will also calculate the cost effectiveness of the different
treatments.
If the theory behind the trial is correct, patients who become PET -ve after induction R+chemo will
do just as well, or even better, without R maintenance, whereas those who remain PET positive will
benefit from the addition of lenalidomide.
If the theory is not correct, patients who become PET -ve may have shorter remissions without
rituximab but should live just as long and have fewer infections. There is also the risk that PET +ve
patients who receive lenaliomide will not benefit and have more side effects but we think this risk
will be low.
In summary, the trial aims to move away from the old “one-size-fits-all” approach to treatment in
which some patients are over-treated and others untreated towards a newer, more tailored
approach that aims to maximise treatment effectiveness whilst minimising side effects.
3