MONOCLE

A clinical trial to test the safety and effectiveness of a new drug, tefinostat, for patients with chronic myelomonocytic leukaemia (CMML).

Background

CMML is an uncommon form of cancer that causes a build up of cells called monocytes in the bone marrow and blood. It mainly effects older people and the average length of survival is only 11-17 months. Most patients with CMML are unsuitable for bone marrow transplant therapy and there are currently very few other treatment options. There is a pressing need for new drug treatments which can target the abnormal monocytes without causing unacceptable side effects.

Tefinostat is a new drug, taken by mouth as a capsule, which only becomes active after it is inside monocytes. In laboratory studies, tefinostat was effective against monocyte tumours and, in a small 'phase 1' clinical trial in 18 bone marrow cancer patients, it was shown to target monocytes without causing side effects.

In this 'phase 2' trial, 40 patients with CMML will be treated at 12-15 hospitals in the UK to allow us to test the effectiveness of tefinostat in CMML as well as monitoring for side effects. Blood and bone marrow samples from patients will be tested in the laboratory to help us better understand how tefinostat works and to identify which patients are most likely to benefit in future.

The research is focused on the need for more treatment options for CMML, specifically treatment that does not cause unreasonable side effects.

Study design

The MONOCLE trial follows a simple Bryant and Day two-stage design which is based on Simon’s two-stage design but incorporates toxicity as well as clinical efficacy (futility) considerations into sample size and early stopping rules in order to avoid unnecessary exposure of patients in the event of excessive toxicity or in the absence of evidence of clinical efficacy.

Given the relatively low numbers of patients treated to date, we feel it is important to now employ a simple single arm phase 2 design to establish safety and efficacy in the context of CMML, building in an early-stopping rule in order to avoid unnecessary exposure of patients in the event of excessive toxicity or in the absence of evidence of clinical efficacy.

Involving the public and patients

We were fortunate enough to work with an excellent patient representative with CMML, who is also professionally experienced at writing scientific information for lay people. She helped us review and adapt our patient information sheets to make them as patient friendly as possible and gave feedback to us from ethics committee comments.

Our patient information sheets are far more patient-friendly and effective after the input from our patient representative. This will mean participants on our trial will be far better informed of the trial and will have a much more positive experience of taking part in research as a result.