Clinical Trials

Trials come in a number of forms - some are financed entirely by pharmaceutical companies as part of their research or quest to get medicines licensed.  Doctors, or groups of doctors can also design 'investigator-led' trials which seek to improve treatment, and often pharmaceutical companies will provide the medicines free of charge.  In both cases there may be strict entry qualifications - for instance having been previously treated - i.e 'relapsed WM' . Some trials will not be specific to WM, and may be open to broader categories such as 'low grade non-Hodgkin lymphoma' . In all cases if you enter a trial you will likely be monitored more closely than if you were a 'run of the mill' patient. All trials have a chief investigator who monitors the opening, recruitment and closing of trials.  Many trials have a relatively short window of opportunity for recruiting.  

In rarer diseases, like WM, trials are especially valuable, but not so common because there is always concern that they will not be filled up.   However WM patients seem very good recently in offering themselves and this is to be welcomed. 

If you feel a trial is an option for you, you will need to discuss it with your doctor.   He/she may not be aware of all trials that are available, or their hospital may not participate, so it's best to do your research first and come armed with as much information as possible. 

Trials are generally classed into into phases 1-4 based on their objectives.   Normally a new medicine will progress from phase 1 to phase 3 trials if deemed successful. 

Phase 1 trials
They are usually small trials, recruiting only a few patients. The trial may be open to people with related cancers. If laboratory testing shows that a new treatment might help treat cancer, phase 1 trials are done to find out the safe dose range, what the side effects are, how the body copes with the drug and if the treatment reduces the cancer. Patients are recruited  slowly onto phase 1 trials. So although they don't recruit many patients, they can take a long time to complete.  In a phase 1 trial, you may have lots of blood tests, as the researchers look at how the drug is affecting you and change doses. They also look at how your body copes with, and gets rid of the drug. They record any side effects. People taking part in phase 1 trials may have advanced cancer and have usually had all the treatment available to them. They may benefit from the new treatment in the trial, but many won't. 

Phase 2 
Not all treatments tested in a phase 1 trial make it to a phase 2 trial. These trials may be for people who all have the same type of cancer, or who have several different types of cancer.  Phase 2 trials aim to find out If the new treatment works well enough to test in a larger phase 3 trial and investigates which types of cancer the treatment works for, more about side effects and how to manage them also about the best dose to use. Although these treatments have been tested in phase 1 trials, you may still have side effects that the doctors don't know about.  Phase 2 trials are often larger than phase 1. There may be up to 100 or so people taking part. Sometimes in a phase 2 trial, a new treatment is compared with another treatment already in use, or with a dummy drug (placebo). If the results of phase 2 trials show that a new treatment may be as good as existing treatment, or better, it then moves into phase 3. Some phase 2 trials are randomised. This means the researchers put the people taking part into treatment groups (arms) at random.

Phase 3 
Phase 3 trials may compare a completely new treatment with the standard treatment, different doses, or ways of giving a standard treatment.  Phase 3 trials usually involve many more patients than phase 1 or 2. This is because differences in success rates may be small. So, the trial needs many patients to be able to show the difference.  Sometimes phase 3 trials involve thousands of patients in many different hospitals and different countries. Most phase 3 trials are randomised. This means the researchers put the people taking part into treatment groups ('arms' of the trial ) at random and each group gets a different treatment to enable comparison.  In some cases, where your WM progresses whilst on a trial you may be switched to another arm.   It is becoming less common for trials to have a placebo arm (no active medication) - one of the reasons for patients opting not to take part. 

Phase 4
Phase 4 trials are done after a drug has been shown to work and has been granted a licence. The main reasons for running phase 4 trials are to find out  more about the side effects and safety of the drug, what the long term risks and benefits are and how well the drug works when it’s used more widely.

There is a very good discussion about trials  on the Cancer Research UK website     Cancer Research UK - trials    Their list of trials is not always up to date, however. Currently only the R2W trial (see below) is featured.


UK Trials Update

Trials are well documented, but they tend to open at different times in different centres as they get local approval, and we want to be able to give both doctors and patients up to date information so welcome further details and feedback from Doctors.  
The UK R2W phase 2 trial (BCR -Bortzomib, Cyclophosphamide, Rituximab)  v  FCR (Fludabarine, Cyclophosphamide, Rituximab) is now fully recruited 6 months ahead of time and now closed, so congratulations to all concerned.  
There is to be an European phase 3 trial 
ECWM1 (DRC Dexamethasone, Rituximab, Cyclophosphamide +-Velcade (Bortezomib).  
 Phase 3 trial  innovate  (Ibrutinib+ Rituximab V  placebo + Rituximab) by Pharmacyclics. (Ibrutinib is the first Bruton's Tyrosine Kinase Inhibitor to be licensed for WM by the EU).  details are at  innovate UK trial sites which are Birmingham, Slough and Bournemouth, but will only be open for recruitment from late October to Late December, so act now!
The Acerta
phase 1b ACE-WM001 (ACP 196- Brutons Tyrosine Kinase Inhibitor) at 6 sites - is also recruiting well according to Dr. Roger Owen at Leeds Teaching Hospital. He is the main UK contact. 

Details of most trials can be found at http://www.clinicaltrials.gov This is an American site, but lists worldwide trials for WM, but is not always fully updated. You may have to dig down under locations to find more detail.  In the past UK WM patients have crossed the Atlantic to take part in USA trials , particularly at Dana-Farber. This is a challenging option, and needs to be well financed! 

There is also an EU trials site  www.clinicaltrialsregister.eu/ctr-search/search?query=waldenstrom and a UK clinical trials gateway at UK Gateway .

If you have any problems then please contact us and we will try to help locate a trials contact.