Dr. Tal Munir on CLL Trial Design in the United Kingdom

I met with Dr. Tal Munir at the CLL Ireland First National CLL Patient & Carer Day Information and Advocacy on Saturday, April 29, 2017 in Dublin, Ireland where I was privileged to be part of the faculty.

Dr. Munir works with Dr. Peter Hillmen and others on the research in chronic lymphocytic leukemia (CLL) organized at St. James Hospital, Leeds, United Kingdom.

The design of clinical trials is critical to their success and the impact they have in CLL management.

We have interviewed Prof. Hillmen before on this topic.

Take Away Points

• There are now multiple new targeted as well as older drugs that works well in CLL.
• The next question is how can we best combine these drugs.
• Another question is ‘Can we find biological markers that predict who will do well and who is about to relapse before the actual clinical event?’
• These are mostly smaller phase 2 trials.
• When there is a sign that a certain combination is working well, a larger phase 3 trial is arranged to accelerate the approval of the drug.
• Such Adaptive Trial Design can help get therapies to patients quicker.

For more on the phases of trial please see this with a link to American Cancer Society.

You can read the transcript of our interview or watch the video below.

Dr. Brian Koffman – Hi. I’m Dr. Brian Koffman. I’m a family doctor, and a CLL patient, and the founder and Medical Director of the CLL Society. And I’m here in Dublin, Ireland for the very exciting launch of CLL Ireland.

Dr. Tal Munir – Hi. I’m Dr. Tal Munir. I’m one of the hematology consultants at St. James’s Hospital in Leeds, UK. And I’m also very excited to be here, to be part of the CLL Ireland meeting today.

BK – First, thank you for coming here and doing this. Second, you’ve been very involved in, not only the research in CLL, but how that research is designed. I wonder if you could talk a little bit about some of the innovative things you’re doing to try to speed up the research in the United Kingdom on CLL.

TM – So as we know, that CLL has seen a transformation and we now have multiple drugs that we can work around. And clearly, individually, these drugs have improved the quality of life for the patients, as well as improved the overall survival in multiple trials. Now the next question really is how well we can incorporate these drugs in combination in clinical trials and try to get the best outcome for our patients, without increasing the toxicity. And in that respect, what we are trying to do in the UK is do very structured focused trials in patients with relapsed refractory disease who would benefit from combination therapy and looking at the biological endpoints in the trial, as well as the clinical endpoints, in order to us to tell us how the things will evolve over time… and then trying to…

BK – Let me just stop you there for a sec. When you say “biological endpoints”, are you looking at biomarkers, rather than waiting for a patient to actually relapse? Is that what we’re talking about?

TM – Well, those are the questions really that we’re trying to ask in those trials, as well that what are the signs that the patients are starting to relapse on these combinations. They are looking at the question of minimal residual disease, looking at other mutation markers, looking at the genome of the patients. It’s all very important because that will help us to design which combination of therapies are the likelihood… will give the best chance to our patients to get into very deep remissions.

BK – And with this kind of structure, do these trials tend to be smaller or quicker to read out the data? Because, you know, as a patient, I’m just waiting for you to publish this stuff. So tell me about that.

TM – Yeah. So, our structure is such that we like to do small Phase II trials to test these combinations, finish the recruiting very, very quickly, and if we see very early signs that actually this combination is safe and there is not much toxicity attached to the combination, then we are trying to incorporate that into our Phase III trials very, very quickly so that we can get these patients access to the new drugs very, very quickly as well as get this data out in a larger trial so that we can get approval for these drugs in combinations quickly.

BK – Any final things you’d want to share with the Irish community, or the UK community, or the world community, of patients in CLL, in terms of the trial design?

TM – I think the most important thing is that adaptive trial design is very, very important. Considering where we were standing six years ago, things have moved on so quickly. The trials need to move on quickly as well.

BK – Yeah, and only by moving quickly with so many combinations are we going to get the answers and I really do think the United Kingdom is leading the way in that. I think that it’s a fabulous model and I wish your colleagues in the US were adapting an adaptive kind of approach. As a patient that’s what I see.

TM – I think, yes, different teams are working in different ways, but I think hopefully we are coming to a very exciting era in the treatment of CLL.

BK – Dr. Munir, thanks so much. Thanks.

TM – Thank you.

 

CLL Ireland First National CLL Patient & Carer Day Information and Advocacy was a hugely successful launch of CLLI (Chronic Lymphocytic Leukemia, Ireland) with a wonderful educational forum similar to the ones we are doing across the USA.

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Dr. Talha Munir is a Consultant in Clinical Haematology at Leeds Teaching Hospitals NHS in the United Kingdom.

Dr. Brian Koffman, a well-known doctor, educator and clinical professor turned patient has dedicated himself to teaching and helping the CLL community since his diagnosis in 2005. He serves as the unpaid medical director of the CLL Society Inc.

Originally published in The CLL Tribune Q3 2017.