Flair trial

[Research123]

Does anyone know when this trial finishes and what the outcome is likely to be? Presumably they are trying different drug treatments - does that mean the nhs will change their treatment protocols and if so when is that likely to be? Thank you!

[bennevisplace]

cancerresearchuk.org/about-...

says that recruitment is due to end 31 Dec 2020.

If so, all FCR subjects should be treated by mid 2021. Patients in the Ibrutinib and I plus Venetoclax arms will carry on longer, some for years, see protocol.

Treatments will be compared primarily on duration of progression free survival and secondarily on overall survival, so many subjects will be monitored for many years yet. I don't know when interim results are expected.

[Research123 in reply to bennevisplace]

Thank you. That is good to know. So I suppose by mid 2021 they will start deciding whether it is best to carry on with fcr or the other treatments? I am wondering why this study is taking place - have there been no such studies in the states where I guess most of these treatments were developed? Or is this basically working together with studies going on worldwide? It seems that in the USA they prefer other treatments now, whereas in the UK they haven't made up their mind yet?

[bennevisplace in reply to Research123]

In this trial patients in the FCR arm are supposed to receive 6 X 28 day cycles of drugs, so by 6 months no more treatment just monitoring. In the other two arms of the trial I believe patients stop treatment once their CLL becomes undetectable. Some patients have had treatment interrupted by Covid.

The USA seems to have largely abandoned chemo immunotherapy (FCR etc) in favour of targeted drugs, including Ibrutinib and Venetoclax, as first line treatment. Clinical trials there, and there are many ongoing, show great promise but have yet to firmly establish the long term (10 years plus) superiority of any targeted drug combination over FCR first line, other than for those patients whose genetic markers make FCR less effective. I don't know if any trial of targeted drugs has generated longer term survival data than Flair, which has been recruiting for 6 years. I'm guessing it will be several years more before Flair has enough data to persuade NICE to give targeted drugs equal consideration to chemo immunotherapy for first line treatment of CLL in the NHS.

[Newdawn Administrator]

Frankly I wonder how accurate results will be if my Flair trial experience is anything to judge by. I’ve not had any specific trial testing done since Nov last year and my follow up flow cytometry and BMB has been in indefinite cessation since the pandemic began. I’m continuing on Venetoclax having had to stop ibrutinib after 15 months with Stage 3/4 arthralgia and myalgia.

This will skew treatment for me as continuation time is dependent on time to reaching MRD status and I don’t know if that happened 8 months ago or not at all (though my blood levels are spot on!) 😊

I don’t think all future first line treatment decisions are dependent on the outcome of this trial however, as important as it is.

Newdawn

[AdrianUK in reply to Newdawn]

The thing is the primary end point is not the bone marrow nor the CT scan but how long you remain well on your treatment. That is still being monitored I presume. At least by you. Unless your nodes are growing or your blood count is deteriorating you remain a success story. And hopefully at some point your hospital will get their services running again.

I am sure that the study will provide high quality data over many years and these Months of covid reorganisation will be a blip. I read somewhere that at one point something like 1 in 4 hospital inpatients were being infected by COVID whilst there. So keeping us away from hospitals for a while did make a lot of sense. Though some places have done a better job of for example organising a district nurse to take bloods at someone’s home if needed and other ways of trying to keep medical assessment and treatment ongoing. As someone who is struggling with a lot of weird symptoms and having to try and explain these over the phone to diffeeent doctors I do understand and share the frustration and hope soon we will be able to return to face to face meetings since I am sure some things are definitely being missed.

As for decisions for the NHS I really do think that if a clear winner emerges then it may change practice. But there are two treatments being considered by NICE as potential first line in the next few months - Acalabrutinib and Venetcolax plus obinituzimab. I rather suspect that if either are approved for a broad group then they will rapidly replace FCR in many patients first line. But how ironic would it be if it turns out that using FCR first before the newer drugs actually gave us the best chance of ten or twenty years or more of relatively healthy life after all. I wonder if we’d ever be able to revert back to that treatment by the time everyone had got used to not using it?

Chemo sounds so much less attractive than selective treatments and we instinctively think they most likely must be better. In the Uk we have a tradition of not simply assuming the new is better and we want where possible to do the head to Head studies for prove which is best.

[Newdawn Administrator in reply to AdrianUK]

I appreciate the importance for me is how well I remain on treatment but from the point of view of Flair data, I’d assume that how quickly patients meet varying milestones is important. It’s certainly featured highly on all other trial studies I’ve read like the Clarity trial etc.

Certainly during the peak of the crisis, non attendance at hospital was very desirable but as with a number of medical services, I think they need to be getting their act together now. Covid patient numbers are low and I was the only person at the drive through Covid testing centre yesterday.

I‘m becoming increasingly frustrated at virtually all services in all sectors using Covid as a reason for failure to provide, treat or investigate!

However I’m probably in a crabby mood presently for above reasons! 😉

Newdawn

[AdrianUK in reply to Newdawn]

Completely agree that it is time for the NHS to really get their priorities straight and sort out the huge backlog of important things that have been missed. I only just got my sleep study result done in FEB and it turns out it wasn't normal as I had assumed! I am also getting some MRI investigations done (tho those are private).

[Newdawn Administrator in reply to AdrianUK]

I’m having to pay a great deal of money for private cataract surgery (this Thursday) because my NHS surgery had to be cancelled 18 months ago because I had a permanent chest infection and cough. Then I started treatment & IVIG to sort the cough. Covid intervened and the list now stretches back to last year! 😳

Newdawn

[Research123 in reply to Newdawn]

I am thinking of getting some laser eye treatment some time - is that not an issue for people on watch and wait do you know? I thought perhaps might be the same situation with cataracts etc.

[Newdawn Administrator in reply to Research123]

I’m on treatment presently but can only have surgery because I’ve stopped my ibrutinib for now. On W&W there would have been no problem unless I had a very low platelet count.

Lots of people on here have had cataract and eye surgery without issue. Something to ask your haematologist about however 😊

Newdawn

[Research123 in reply to Newdawn]

Thank you. Hope all goes well with the surgery. Cataract surgery has changed the lives of everyone I've known who has had it.

[Newdawn Administrator in reply to Research123]

Thanks Research. People tell me that so hoping all goes well.

Newdawn

[annmcgowan]

Hi I am in flair on ibrutinib only arm. Ibrutinib is a control rather than a cure drug so rare if ever reaches MRD (-).

My understanding is that the FCR arm of the trial was stopped a while ago.

Ann

[Newdawn Administrator in reply to annmcgowan]

I hadn’t heard that Ann. Would be puzzling if it was and we’ve had new FCR patients on Flair post on here very recently.

The ibrutinib and rituximab arm was closed some time ago.

Newdawn

[annmcgowan in reply to Newdawn]

Sorry my mistake.

Ann

[AdrianUK in reply to annmcgowan]

I am pretty sure that is not the case. As they explained to me that the primary end point for each arm is how it compares to FCR not each other. So you have to have FCR patients in the current randomisation to make it a fair comparison. As I understand it the only reason IR was stopped was that it enrolled sufficient numbers early on because it was initiation just FCR vs IR I believe. There was a period of time though where nobody was enrolled into FLAIR due to a desire not to start anyone on FCR in the height of the pandemic. Maybe that was the source of whoever told you the FCR was stopped since of course those on the other arms would still e being treated throughout.

[annmcgowan in reply to AdrianUK]

Sorry my mistake.

Ann

[Wiganmc in reply to annmcgowan]

Hi Anne I personally started FCR on flair trial ten days ago stay safe Tony

[annmcgowan in reply to Wiganmc]

Hi Wiganmc thanks for your reply. My mistake I was thinking of the ibrutinib and rituximab arm, as Newdawn rightly pointed out. I was having a muddle headed day which I get occasionally, don’t know if it’s ibrutinib related or not!!!

Good luck with your treatment.🤞

Ann

[Wiganmc in reply to annmcgowan]

Hi Anne muddled head is a good outcome.,and thanks limited side effects at moment good luck

[annmcgowan in reply to Wiganmc]

👍

[avzuclav]

If we are making predictions on the outcome, I think the table in this post has some useful clues. healthunlocked.com/cllsuppo...

Based on the large numbers in the E1912 trial and all the historical data for FCR, it seems highly probable that all three ibrutinib arms will have better median PFS than FCR.

The good news for everyone is that it will probably take decades to determine which arm has the best median overall survival.

My understanding is that they stopped the ibrutinib+rituximab arm after it was shown that adding rituximab did not improve PFS:

ashpublications.org/blood/a...

[Research123 in reply to avzuclav]

Thank you that's some great info