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Wales Cancer Research Centre,
Room 1TB2 31,
First Floor Main Building,
University Hospital of Wales,
Cardiff, CF14 4XN
18 Dec

Researching treatments for rare blood cancer

MONOCLE CMML lukaemia trial - white blood cells

Chronic myelomonocytic leukaemia (CMML) is a rare type of blood cancer where there are too many monocytes (a type of white blood cell) in the blood.

Around 450 people develop the disease in the UK each year, but there are few treatments. The disease tends to affect the elderly who cannot tolerate aggressive chemotherapy treatments. Allogeneic stem cell transplant is a potentially curative treatment, but this is only possible in a small minority of younger and healthier patients.

Tefinostat is an oral treatment, that selectively targets monocytesand was tested against CMML in a Phase II trial, known as MONOCLE. The trial, which has recently closed, was led by Chief Investigator Dr Steve Knapper, who leads our early phase trials research. It is a great example of research led from Wales as it was managed by the Centre for Trials Research and followed on directly from laboratory work conducted at Cardiff University.

Dr Joanna Zabkiewicz worked with Dr Knapper on initial laboratory work that led to the drug being trialled in patients. She said, “We were very pleased to be able to transition our initial Tefinostat pre-clinical work into the MONOCLE trial, funded by Bloodwise. It is key to my role to have the potential to have patients benefit from the work that we do. I was also involved in the MONOCLE trial management group. Until now, trial management teams have mostly consisted of clinicians and trial managers, so having scientific input into the trial endpoints and sampling in MONOCLE created a more diverse team.”

The trial aimed to determine the tolerability and safety of the drug Tefinostat. Unfortunately the trial didn't show enough clinical responses so was closed after 21 patients had been treated. It is always disappointing when new treatments don’t work as effectively as we might have hoped, but stringently testing them in a clinical setting like this is a vital part of research.

Despite the negative clinical results, there is still more we can learn from the trial.

Dr Zabkiewiz added, “The trial allowed us to collect samples from patients for use in further research - something we now plan to do through a clinical fellow post. In collaboration with some of the clinicians involved in the trial, we aim to study some of the mechanisms of drug resistance for this patient group to help us better understand the biology underpinning the disease. This will improve our understanding for future combination therapy design. So, from a science point of view, there are positives. We made some inroads into being involved in the running of the trial, we undertook the trial associated assays and plan to use the data and the samples to further our understanding of this difficult to treat disease.”

Dr Knapper said, “MONOCLE may have closed, but we are working on plenty of other innovative trials in Wales. As an example we have recently become the only approved Phase I site in the UK for Novartis blood cancer trials.

“AML is another rare type of leukaemia with few treatment options. We’re currently working on a Novartis trial that aims to block proteins that stop the immune system from attacking cancer cells. We’ve recently recruited 11 patients to this study (CPDR001X2105) which makes us amongst the top world recruiters. We’re also proud to be delivering this trial as it is the first trial of its kind that has been made available to AML patients in Wales.”

The outcomes of the MONOCLE trial were presented as an abstract at the American Society of Hematology (ASH) meeting in San Diego in December and a paper will follow in 2019.