Part of my job is leading the early phase clinical trial programme in lymphoma research here at UCLH.
This is a really exciting part of my job
because it allows me to potentially offer exciting new treatments to patients with lymphoma.
This is often in the relapse setting,
where standard treatments have failed to get control of someone's lymphoma,
or perhaps it's come back or relapsed after a number of lines of previous therapy
and the people looking after the patient, whether that's here at this hospital or another referring hospital,
have decided that the current standard treatments no longer offer a chance of treating a patient's lymphoma successfully.
Phase one trials are essentially the first step in testing
whether a new anti-cancer treatment is effective and safe in patients.
The key to phase one trials is understanding that it's about really assessing the safety,
the tolerability, the side-effect profile and optimal dosing of a new anti-cancer,
or specifically in my case, anti-lymphoma, treatment.
The other key difference to phase three trials, for the patient, is that these are quite intensive trials.
These involve a lot of visits up to see us, to see either myself or one of my colleagues.
This may be to look for whether there's any new side effects,
whether they're symptoms that a patient may report, or to look through blood results, blood tests.
There's often quite a lot of blood tests required within a phase one trial to look for side effects,
but also sometimes to measure how much drug is in a patient's bloodstream at any given point in time
after a treatment has been given.
The frequency of visits is quite intense and does need to be taken into account when enrolling a patient in a trial.
One of the other key differences of phase one trials, to say, phase two and phase three trials,
is that these trials have a limited number of patients.
We're really looking for an early signal of safety and tolerability, and hopefully a signal of efficacy as well.
So these trials are looking often to only recruit a small number of patients, often over quite a short time scale.
One of the challenges of the early phase trials is that it's a constantly shifting area,
where a trial may only be open for a short period of time in our centre until recruitment has been achieved.
Another key difference between the phase one trials and phase three trials is,
whereas a phase three trial may be open for a number of years and the site is free to recruit patients
at the rate at which they see patients,
phase one trials go in a stop and start pattern, especially when a phase one trial is starting out
and we're just establishing the safety of a new drug and the optimal dosing of a new drug.
We talk about 'slot availability' and 'cohort dosing' quite a lot in phase one trials.
Both of these concepts mean that slots are available for patients often only in a short time window.
When I get referred a patient I need to consider whether there may be a slot available for a patient
and that will be determined by the sponsor
and it will also be determined by where we are in what's called the cohort dosing.
Often we'll enroll three patients at a low dose, stop recruitment at that point,
watch those patients very closely over a period of time for the development of any side effects or toxicities,
and if no side effects or toxicities emerge, the sponsor will then allow us to open up to the next cohort,
often at a slightly higher dose.
We then are often allowed to recruit, for example, three more patients at the next dose,
at which point recruitment again closes until those three patients have been assessed again
for the safety and toxicity.
This process continues until we see a side-effect or a toxicity
that tells us that perhaps the optimal dose of this treatment has been reached
or sometimes even exceeded.
First in man studies are where a potential new anti-cancer treatment
is used for the first time in human subjects.
This may sound very daunting but I'd be reassured that we only do first in man studies
where there is an absolutely sound scientific rationale for testing a new drug in patients
with relapsed or refractory lymphoma in whom there are no other treatment options.
These drugs will have gone through rigorous testing in the lab
to make sure that there's a good reason to believe it may work in the particular type of lymphoma we're looking at
and to get as good an understanding as we can about the potential side effects or toxicities
experienced with this drug.
The other really important thing to understand about a first in human study
is that we start these treatments at an extremely low dose.
The lab studies will have already established what we think may be the effective dose
but when we're first dosing these treatments in human subjects, we take this right back to a much lower dose
just in case there are side effects that are unforeseen from the lab studies.