Idelalisib Trial frozen!

[Aklambert]

Was starting a trial on Monday with Idelalisib. Today I've been told the trial has been frozen. Have to discuss with the team at Birmingham next week. MRI and CT scans, and Bone marrow tests all done in the last couple of weeks. Naffed off To say the least!

[Bubnojay]

Oh no, naffed off hardly covers how you must be feeling.

Hope something advantageous gets sorted.

Bubnjay1

[PaulaS Volunteer]

As Bub has just said, I'm not surprised you're naffed, Aklambert. But it could be that something even better works out for you.

I'd be very interested to hear why the trial has been "frozen". I was on a trial (CALiBRe trial) with Idelalisib last year. It was run from Birmingham. I had to stop after 8 weeks because I got a nasty rash, that led to other complications.

I hope the scans and bone marrow tests you've had done, won't need to be repeated if you go into another trial soon. Before I was accepted on CALiBRe trial, I was going for "Iluminate" trial and had all the tests done for that, but then was told my nodes were not large enough to qualify for "Iluminate". So, I changed to CALiBRe, and some of the tests were OK for that.

Best wishes,

Paula

[Aklambert in reply to PaulaS]

Thanks for your kind words Paula. I'll post after Wednesday when I know more. My trial nurse said my consultant was still waiting for a conference call to find out why it's been frozen. So they're in the dark as well

[Debinoz]

I'm afraid the reason is patient deaths on several of the trials. This from Dr Furman on the CLL Acor Listserv. Frustrating for us all but so tragic for those involved and their families particularly given these were treatment naieve cohorts and phase 3 trials and I would feel safer being on one of those than the phase 1 trial I'm on. Here's what he said

"There has been several announcements made regarding idelalisib (Zydelig) over the past several days. In essence, there was an increase in deaths in several studies in the patients receiving idelalisib compared with placebo. These deaths were mostly infection related and seen in patient who had received minimal prior therapy. As a result, several idelalisib trials involving treatment naïve patients are being closed.

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> For those already on idelalisib and receiving benefit, this should not necessarily result in you changing your treatment plan. This is something to discuss with your physician. The official recommendations will likely involve using prophylaxis for PCP and monitoring for CMV.

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> Rick Furman

[Cllcanada Top Poster CURE Hero]

This is a tragedy, and clinical trial investigators need to do some soul searching...

It is important to understand these problems are in combination trials using Idelalisib (Zydelig) in combination with another UNAPPROVED treatment for CLL according to the EMC.

Since Dr. Furman points to PCP and CMV, I suspect the trial is the Idelalisib (Zydelig) and Gazyza verses Gazyva and Chlorambucil trial currently running in Europe...

clinicaltrials.gov/ct2/show...

PCP and CMV are adverse events seen in all CD20 monoclonal antibodies... but it was also seen in Idelalisib (Zydelig) trials..

sciencedirect.com/science/a...

Gazyza is not approved as a single agent in CLL

~chris

[Justasheet1]

Chris,

I gently disagree. Though you could be correct, I believe it's the status of being treatment naïve causing these issues. From all that I have read and experienced this is what I point to.

I was on prophylactic meds and still had issues. I knew what I was choosing when I started but still thought being a phase 3 trial they had ironed some things out.

I'm happy I received BR with the Idela because I was treated and can enjoy my remission from the chemo and hope the 15 months of Idela gives it more punch.

Again, bigger minds than mine will sort this out.

Jeff

[Eagle5327]

Don't blame you in the slightest for being POed, as we say on this side of the pond. Very frustrating. Hopefully your course of treatment is well laid out for you even without the Zydelig.

For what it's worth, I think you might have been lucky. I was part of a trial last year for previously untreated patients that included idelalisib. The trial was a two-armed random study that featured bendamustine and rituxumab for both arms, plus Zydelig in one arm and a placebo in the other.

It became obvious within a week that I had received the idelalisib and not the placebo. About 70% of people who get Zydelig do very well on it but 30% or so don't. I had an absolutely horrible time with it.

The first sign of trouble was that within a week severe diarrhea and extreme abdominal pain showed up, far beyond any abdominal pain I've ever felt. The second sign was that I passed out soon afterward from the abdominal pain and had to be taken to the emergency room. Spent all day there and had to come back to the hospital for the next two days for steroids, hydration, and observation.

The worst thing of all is what it did to my liver. Liver numbers were approximately 100 times normal and I felt terrible.

All treatment was discontinued for about two months until my liver numbers came down. Then the trial protocol called for restarting the BR plus a reduced dose of Zydelig. We started again at the reduced dosage.

Within 24 hours I had passed out again from the pain. It was awful. Back to the hospital I went. After that, the Zydelig was discontinued. When my liver numbers finally came back down again, the BR was restarted and I completed all cycles.

End of the story is great: I got a very good partial remission and feel far better than I have in over a year.

At first, I was very excited to be a part of this trial because I wanted the Zydelig and was afraid of the BR. The end result was the opposite. The old fashioned chemo-immuno treatment was effective and easy for me to tolerate but the new super-duper targeted drug was by far the worst. In a way, the trial was a success because Gilead got an enormous volume of adverse data from me. I am not sorry that I enrolled and gave it a go.

Assuming my remission relapses, which it probably will, I don't fear the consequences. I'll have plenty of excellent choices. I will almost certainly enroll in another trial to help the research move along as quickly as possible.

I'm so sorry for the awful frustration you're feeling. Hope some of this helps a little.

I wish you the very best of good fortune and good luck as you go through treatment. Hang in there and be well.

Geoff

[Cllcanada Top Poster CURE Hero]

I have spent the day researching this and there is one CLL trial and two NHL, that have been put on hold

Here are the details from the EMC...

GS-US-312-0123; GS-US-313-0124; GS-US-313-0125

Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab in Subjects With Previously Untreated Chronic Lymphocytic Leukemia

clinicaltrials.gov/ct2/show...

Efficacy and Safety of Idelalisib (GS-1101) in Combination With Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas (Yosemite)

clinicaltrials.gov/ct2/show...

Efficacy and Safety of Idelalisib (GS-1101) in Combination With Bendamustine and Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas (Bridalveil)

clinicaltrials.gov/ct2/show...

~chris

[Justasheet1]

Chris,

I wonder if there will be a trickle down to the new P13K inhibitors like the TGR and IPI stuff.

I was in the first study you mentioned. I failed it. I had everything but the colitis that was listed on the black box warning.

Jeff

[Cllcanada Top Poster CURE Hero in reply to Justasheet1]

I don't know... there isn't a full understanding of how these actually work, so any addition knowkedge will benefit future generations of these drugs...

PCP and CMV, are controlled by T cells... so it might be a good place to start...

I had a mild case of PCP in 2007, very unpleasant...

[Cllcanada Top Poster CURE Hero in reply to Cllcanada]

It might be that treatment niave patients have better T cell function, so Idelalisib (Zydelig) works better and impacts the T cells in a negative manner and causes these immune problems...

Previously treated, generally have poorer T cell functions, so the effect on them is reduced... in theory

I recall something about p110 on T cells and Idelalisib in mice way back in the CAL-101 days... it will be interesting to see how this is resolved, likely steroids and prophelactics, perhaps a reduced dose.

~chris

[Justasheet1 in reply to Cllcanada]

Chris,

Using me as an example and understanding everyone is different.

I was on Bactrum and Acyclovir. I was stopped several times and finally dose reduced and still would get elev liver enzymes and a cough that was suspicious of pneumonitus that always resolved with prednisone.

Treatment naïve with BR + Idela. My white count was doubling with big nodes when I began.

It seems my issues were autoimmune in natures so I believe it is the T cells.

Jeff

[Justasheet1]

Dr Koffman says it best in CLL Society

cllsociety.org/2016/03/ash-...

Jeff

[DeletionLady]

I have been on Zydelig (Idelalisib) since January of 2015. It began with 8 weeks of Rituxin infusions. I have not had a single side effect other than itchy skin in the first month. My WBC counts have all come down to - and remain in - the normal range. In January 2015 my WBC count was in the high 300's. All swollen lymph nodes - external and internal - have shrunk significantly - none on my neck or groin.; the spleen is normal size. My CLL is considered - cautiously - in remission. So the decision on the part of Gilead Sciences to stop the trial immediately for ALL patients is a bit of a set-back for me. I'm back to square 1 - watching blood cell counts and lymph nodes rise again (??). My oncologist is a CLL specialist - so we'll see what's in store for me.

[Justasheet1 in reply to DeletionLady]

We're you treatment naïve?

[DeletionLady in reply to Justasheet1]

As a newbie to these posts, I'm not quite sure what naive means but - this was the first line of treatment for me after a year and 7 months of wait and watch. When, after a year, it was determined that I had the chromosome p17 deletion, my oncologist referred me to a colleague who 'specializes' in that variation. After scrutinous testing, I was considered a "good candidate" for the trial and it has been effective in not just tamping down further WBC growth but getting all my numbers in normal range.

[AussieNeil Administrator in reply to DeletionLady]

Treatment Naive means not previously treated. You did well finding an expert that put you on a non-chemotherapy treatment such as Idelalisb, as with a 17p deletion, you'd likely only have a short remission on an older treatment.

Neil

[DeletionLady in reply to AussieNeil]

Thank you Neil - that's what I suspected it meant. I had reached the place where I was seeing the oncologist (and oncology team) once every eight weeks (down from weekly then bi-weekly, then monthly) and was headed toward 3x per year, but since the abrupt trial shutdown by Gilead, he's bringing me in this coming week and I'll see what the options are going forward. Needless to say, it's quite disappointing especially since it brought my cell counts back down into normal range. He fought VERY hard (understatement!) to get the trial approved at the hospital and I was the first patient there to start the treatment. Of the 3 additional patients that also participated, I was the only one that had such positive results; the only one that remained on the trial. They're also taking a look at why my body responded differently from others in the trial (cells, genetics, metabolism...??).

I found this community while googling around trying to get details about the trial shutdown. With the death of a close family member a year-and-a-half ago of complications from Multiple Myeloma traumatizing my family, I opted to only tell 3 people (my son, my sister and one sister-in-law) so it's good to have a place to talk and share.

[AussieNeil Administrator in reply to DeletionLady]

Thanks to your involvement in the Idelalisb trial as a treatment naive patient, you may well be able to help many future patients if the experts can unravel why you did so well. That's a nice reward to your oncologist for his efforts on your behalf and thanks on behalf of our community too.

You may be able to continue on Idelalisb with additional antibiotic prophylactics or you could switch to Ibrutinib. Let us all know how you go.

Neil

[DeletionLady in reply to DeletionLady]

Will do!

[AussieNeil Administrator]

'All patients given the cancer drug idelalisib (marketed as Zydelig) should be prescribed antibiotics during treatment and for two to six months after treatment has ended to prevent pneumonia, according to a new Europe-wide proposal.

Following a safety review of the drug, the European Medicines Agency’s Pharmacovigilence Risk Assessment Committee (PRAC) says patients taking idelalisib should be monitored for infection and have regular tests for white blood cell counts, because a low reading indicates increased infection risk. It also says idelalisib should also never be started in patients with a generalised infection.'

pharmaceutical-journal.com/...

[greygirl in reply to AussieNeil]

now I`m scared. My oncologist wants to do rituxan/zydelig. I`ve had a ongoing sinus condition that has not cleared with antibiotics since I had FCR 2014-2015. I was told this sinus condition would go away once starting ibrutinib. But while on ibrutinib I had constant yellow mucus come out which was not as bad as the rashes, joint swelling and pain non stop for almost two months. After having to come off ibrutinib I had about a week and a half of relief from this stuffy nose/ yellow mucus issue and now it`s back. I wonder what impact this will have if I decide I only want to take zydelig without rituxan as all this trouble started with rituxan in the first place. got any ideas anyone?

[Justasheet1 in reply to greygirl]

Greygirl,

Can you get it without Rituxin?

I would find a good ENT and get this sinus thing straightened out. You need to hit the bear hard. You've been through FCR, Ibrutinib and now Zydelig.

Perhaps you need to have your immunoglobulins checked?

Jeff

[greygirl in reply to Justasheet1]

Thanks for reply. I haven`t tried zydelig yet. took antibiotic. didn`t work I went to an ENT. said bacterial infection. I had levaquin for ten days. cleared up short time. then came back. told once on ibrutinib go away. instead mucus flowed more While taking ibrutinib got infection on hand -on another antibiotic ten days- cleared up infection only put small dent in sinus thing. my iGg`s have gone down since FCR that`s for sure. Big war waging about immunoglobulin treatment on other cll sights! I go oncologist in 12 days about either restarting ibrutinib or zydelig. thanks for imput.

[AussieNeil Administrator in reply to greygirl]

Share your concerns with your oncologist so that you will be monitored more carefully. Unfortunately with CLL, to get the best out of treatment, it is often a case of having to carefully manage side-effects and the possible impact on co-morbidities. This is where being able to see a CLL specialist is worth the effort if at all possible.

If your oncologist did decide to change your CLL treatment, it would most likely not be as effective and you'd likely have a shorter remission time...

Neil

[greygirl in reply to AussieNeil]

I was being monitored every week but not sure my doc was looking at side effects. Was enduring 2 tabs of ibrutinib but doc alarmed by wbc going up. No suggestions of pain meds until the end and I`ve thought of specialist but tied to my insurance and you know what that means for affordability but I`m getting good feedback from different people so hopfully can make an informed decision. I`ve survived thus far. The most important thing I`ve learned is stay calm and don`t rush into anything. About the remission, who knows how long I would have been in remission on ibrutinib? So many have had up to five treatments and I`m only on my second with a whole bunch to choose from. Sharing my concerns with my doc is hard when you are only given about a half an hour or so of his busy schedule. But I`ll try again. Thanks.

[AussieNeil Administrator in reply to greygirl]

Hi Greygirl,

It would really help members responding to you if you could update your profile to include your treatment history: healthunlocked.com/user/gre...

(I for one am finding it difficult to understand what you've been through from the snippets mentioned in your replies.)

When you say 'Was enduring 2 tabs of ibrutinib but docdoc alarmed by wbc going up', I presume you mean your regular GP, not your oncologist? In either case, this has me concerned about the adequacy of care you are receiving, because with Ibrutinib, the WBC regularly goes up due to lymphocytosis - CLL cells flooding into the blood stream from lymph nodes. Only a minority of people on Ibrutinib don't experience this. Your oncologist should know your WBC will most likely go up and should have informed you and your doctor.

Lymphocytosis in patients taking Ibrutinib has been well studied, including research into a subgroup of patients who had extended lymphocytosis lasting longer than 8 months per this paper on prolonged lymphocytosis: bloodjournal.org/content/12...

From the abstract of this paper (with my emphasis):

'The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib has outstanding activity in patients with chronic lymphocytic leukemia. Most patients experience lymphocytosis, representing lymphocyte egress from nodal compartments. This resolves within 8 months in the majority of patients, but a subgroup has lymphocytosis lasting >12 months.'

Seriously consider arranging for a second opinion before you accept any recommended changes in your treatment.

Neil

[greygirl in reply to AussieNeil]

Yes, l actually went up from 44.000 to 88.000 then up to 168.000 with the changes in dose. It was when l started to go down while on 3 tabs but when switching to 2 tabs my count started to rise rise again and my oncologist was the one who was worrying about this. As I said l was still learning all the ways ibrutinib acts and getting feedback from everyone and my own endless research and now with this knowledge maybe I can go back and try ibrutinib again.