ImetelChat

The pilot study has been updated Oct 5th in a seemingly innocuous way, just the addition of FDA on line 2. But why? This study has been on auto pilot for a while and Irish's husband has been forced to travel long distances for the drug that is basically available down the block. The pilot study has 81 patients listed with top line data scheduled for May 2017 (and enrollment starting 2012). 81! Only 33 were reported so far. Some are MDS/AML but the rest have not been reported to my knowledge. With CR and PRs and CIs clear from a researcher and institution (Teferri/Mayo) above reproach one must wonder what gives? The FDA has said they will approve for unmet medical needs on the basis of small studies in specific circumstances. If not this than what? bp

Mysterious indeed. For sure a lot of data are being collected.

Another thing which is not clear to me: only 7 sites from the long list of Imbark pilot sites are not yet recruiting. All the others are! What happens to those who are being recruited? Waiting months and months to finally get the first dosing? These people are very sick, have no options nor time. Is there another MF trial in the making? One that targets a broader group of MF patients?

Fish, I don't think the CT site now reflects the fact that these sites are no longer recruiting, even though the study. The site will probably be updated soon to reflect this consistent with Scarlett's update. bp

These 7 sites were not recruiting YET. What I meant was more all these other sites, who are recruiting. Some of them for quite some time. What are they doing with those recruited patients? I know the CT site is not very reliable in all details. But according to the decission to suspend further recruitment they should officially need to change the status of all these recruiting sites from 'recruiting' to 'not recruiting' or to 'active but not recruiting'.

Btw: the Mayo pilot study already did have a Data Monitoring Committee from the start (DMC, see previous discussions).

Fish, agreed, they should change the site and update it in a timely way. If I were a desperate patient surfing for a clinical trial I would be elated to find the study only to then find out it was really in a state of suspension re enrollment. The patients they recruited up until the update were probably allowed to enroll so I doubt there is a "back log" of patients waiting to get into the study at this point. If I were a patient and the study stopped enrolling before I could complete the screening process I would be profoundly disappointed (and justifiably angry--I am sure the company took those cases into consideration). bp

You are right about the DMC--I wish they would stop the study already for efficacy in the face of an unmet medical need! bp

My thoughts on pilot study in response to discussion:

1. I think the pilot has not been updated in any meaningful way on the CT site. It is pretty much on autopilot with those left from the 33 subset. I doubt we will ever get data on the 81 patients as many left with the FDA hold and disrupted the study. I would like OS data to date on the patients remaining after FDA hold but not expecting it. I think NEJM is what we get. But I could be wrong - I am hoping for some late breaking abstract at ASH. Regardless, I think this trial will now close with FDA approval of imetelstat or not. As I say current study is our 'ride or die'. I think unmet medical needs targets jakafi going forward - as in jakafi not meeting needs - so imet better because it meets unmet need. My highly speculative opinion only.

2. I agree the 7 sites are not recruiting YET. Probably waiting on their IRBs and other logistical/operational components. No one is recruited until ready to accept so unlikely any patients waiting in wings. This would be too cruel for even big Pharma trials. And, in Imbark, you could go to any open center and then transfer closer to home when another site opens. Not ideal - but plenty of centers means many more options for Imbark patients than for original patients still in the pilot at Mayo only.

3. No idea if any wider studies because JJ holds information tightly - but I don't think so. I think we are 'all in' on Imbark and Imerge. I hope no more studies are needed after these studies. But who knows?

4. Yes, Imbark should eventually 'read active not recruiting' but always a time lag for CT site updates. Actually very few patients themselves use the CT sites (although they should). They more typically get referred to trials by their local oncologists - the knowledgable ones who keep up.

5. I imagine persons in Imbark screening process (unlikely many patients as screening is very quick!) would be approved to move forward. Entry could be deemed upon application to study pending confirmation of qualifying criteria. Like voting - if you are in line when polls close you are not turned you away. Shopping, too. Just get in door.

John just back from Mayo. He is very good. All blood counts close to normal or baseline, no increase in circulating blasts, other prognostic indicators like LDH stable, and slow increase in one liver enzyme only as expected and common in many cancer treatments with liver damage associated with disease itself. Minor cost-benefit. All liver enzymes returned to normal during his voluntary treatment hiatus.

He no longer drinks a beer at the ballgame or his favorite scotch - in the interest of science - because alcohol results in same enzyme increases. Went to a wedding - no drinks for John - but more dancing.

He just completed his 36th imetelstat infusion since April 2013.

Regarding the IND 1951 (pilot study) recent change on CT form, Line 2 (regulatory authority), now specifies as bio pointed out: 'FDA'. Perhaps (a very big perhaps), it relates to collaborative work of FDA and EMA with FDA as lead agency - if pilot data might be used at some point for European approval?

Just inviting debate and discussion. Perhaps (a very big perhaps), not innocuous...or do we supersize any scrap of new information?

http://www.ema.europa.eu/docs/en_GB/doc ... 089257.pdf

irish: that could be very well possible. All this testing should lead to something. Mayo, JnJ and FDA now must have quite an interesting amount of data, which is not generated to be ignored. All this testing has cost ten's of millions so far, with many patients on the drug. There must have been some processing and interpretation behind the screens. Soon we will learn what they have decided based on concrete actions (such as changes in the CT site).

Fish, can you shed some light on what "line 1, line 2" type entries are and why the change? I can't find it anywhere. It is a seemingly small change that might just be record keeping, but reading a study should be transparent and straightforward but in this case (and others) it is certainly obscure. bp

Fish and Bio - One fact we do know. A large amount of data over a long period of time was collected and is in the vaults. And, they keep collecting it.

Thanks Irish, I agree they should have plenty of data. Hoping we can see some of it at ASH. Fish Re DMC, the pilot study does not appear to have one but the Imbark and Imerge studies do. Go figure. bp

Bio: the pilot Mayo study (NCT01731951) does have a DMC as from the start. In the normal view you won't see it. But if you display the changes and then make sure nothing is hided, you will see that there is a DMC( <has_dmc> Yes). IMbark on the contrary has no DMC yet (<has_dmc> No). I don't know why IMBark has no DMC, probably because the study is not in the process of moving into Phase 3 yet (like IMerge). The Mayo study is not set up for the approval process I guess.

Fish, right you are, I stand corrected, thanks bp