WIN trial -DNA vaccine +WT1

Hi Chrissie

I am aware of a few trials of CML vaccines aimed at "mopping up" residual disease in patients who otherwise have a good response, just can't quite get to CMR. This is an active area of research, with some promising results.

Perhaps get in touch directly (Sandy has my email address) and I can see if I can find out bit more about the particular vaccine you are being offered. Many think this is indeed the way to elicit the better responses in those with good response already but need a bit more of a boost to get to the best result.

Gut feel says that if the Hammersmith is involved, it's a good thing.

Richard

Hi Chrissie,

Yes I am aware of this trial

http://clinicaltrials.gov/ct2/show/NCT01334060

and have had some (very little) anecdotal feedback so please do not take this as how things are/would be for everyone.

As far as I understand, the feeling is that this might well be curative. It is however, not the normal vaccination we usually think of and is delivered every 4 weeks with an electical impulse into the muscles of both arms.

1mg/dose/vaccine The DNA vaccine will be administered 6 times at 4 weekly intervals. Responders (Immunological but without molecular progression) may continue vaccination 3 monthly to maximum of 24 months.

The vaccines will be injected intramuscularly (im) followed by electroporation (EP) into separate locations.

This electroportation (EP) part can be quite uncomfortable for some people I believe, but then it depends any one individuals pain threshold -e.g as with a bone marrow biopsy-.  

The seduction is in the word CURE..,, and it seems that this might be worth the discomfort. I know there are at least 2 on the trial at HH but I am not aware of who they might be or whether they read this forum.

This is an open label, single dose level, phase II study in two patient groups 1. CML and 2. AML using genetic randomisation.

Consented and eligible HLA A2 positive patients will be vaccinated with two DNA vaccines and

HLA A2 negative patients will be followed up with molecular monitoring only.

The objectives are to evaluate:

1) Molecular response following p.DOM-epitope DNA vaccination in patients with CML (BCR-ABL, WT1) and AML (WT1) at weeks 4, 8, 12, 16, 20 and at months 6, 12, 18 and 24.

2) Time to disease progression, 2 year survival rate (patients with AML)

3) Correlation of molecular responses with immunological responses.

Primary Objective: CML: Molecular response of BCR-ABL.

Inclusion: for CML Patients with PH+ CML in chronic phase in CCyR with (detectable bcr/abl) maintained on imatinib monotherapy for minimum of 24 months.

Locations UK: Royal Devon and Exeter NHS Foundation Trust- not yet recruiting.

                     Imperial College NHS Trust (Hammersmith Hospital) - now recruiting.

                     contacts: Christos Paliompeis email: c.paliompeis@imperial.ac.uk

                                    Prinicpal Investigator, Katy Rezvani email: K.rezvani@imperial.ac.uk  

                     Southampton University Hospital NHS Trust- now recruiting.               

Talk more to your doctor- the person I talked with about this (not a patient) seemed very positive about the possibilities. I think the initial period of vaccination is for 6 months, followed by a further period if there is a good response. 

I will try to find out more- but this is in phase ll and really the data will be driven by people volunteering-i.e taking a chance - just like the first trial patients back in 1998/9 in the phase l and ll trials of imatinib- and look how brilliantly that turned out!

Best.. Sandy

Many thanks for your responses so far. The factsheet I have been given bvy the Exeter hospital is extremely detailed, so I am up to speed with the procedures. I think my main problem is that no one knows what to expect in terms of side effects and I can't think of what questions to ask other than "What happened to the mice?" I am guessing that the trial wouldn't be extended to humans unless the researchers are pretty sure it's safe. As I said, I am inclined to go for it ( otherwise, in future years I may be kicking myself for missing the opportunity).  However, I'll wait a little while to see if anyone on this site who is having this treatment responds.

Will keep in touch

best wishes

Chrissie

Hi Bryan

Thank you for your response. The fact that you say that you are at work has somewhat eased my concerns about this trial!! I look forward to hearing more about your experiences.

Many thanks for replying

best wishes

Chrissie

Hi,

Sorry for being brief earlier. So I think I heard about this trial from a link on CMLSg 9 or more months ago perhaps and mentioned it with the consultants at Hammersmith where i'm treated. So I was diagnosed Nov 2007 and started on Imatinib 400mg. Response was "sub-optimal" so moved up to 600mg perhaps 12-18 months ago and PCR has been stable around the 0.08-0.09% for the last 6 months or so... When I spoke to the consultants at Hammersmith, they did seem very interested in this particular vaccine trial, which I think is very encouraging.

As i'd expressed an interest in this vaccine, I got a call about 3 months ago from one of the doctors running the trial at Hammersmith, who I spoke to at my next visit. So it is a phase 2 trial, and I understand that it has already been tested on a small group of patients, and they want to scale it up to see if the results are statistically significant, which again sounds very encouraging to me!

I understand entry to the trial is if you are HLA A2 and have been on the same medication/dosage for at least 12 months. I had a day (22nd Nov) where it was a day of tests - ECG, echo, chest x-ray, quite a few tubes of blood, bone marrow aspirate (not biopsy!) and apherisis (to spin off the lymphocytes). This is really to give them a baseline. Had my first vaccine on the 28th Nov. The plan is to have monthly vaccines for 6 months, then 3 monthly for 2 years if there are positive results. I think the first 6 weeks they want to see you every 2 weeks for blood tests/vaccine, then monthly for 6 months, then every 2-3 months after that.

So the vaccine itself. It's delivered by a machine which when I asked my consultant said "it looks like a gun!". This is connected to a small machine, and is really so the vaccine and the electropolarisation (electric shock) is delivered in a consistent way. There's 2 small syringes with the vaccine that are put into the "gun". Although they have long needles, they really only go in as far as, say, the flu jab. They're probably 1-2 cm apart. It's all quite simple - the doctor holds the "gun" to the top of your arm, then presses a button on the machine to start the sequence. This inserts the 2 needles in, then a short beep goes off and a current is passed twice between the 2 needles. This is 2 jolts, but the whole thing is over in a second or 2. They then do the other arm. I've only had 1 so far (next on 4th Jan). The injections weren't too bad - probably the same as getting the flu jab x4 (2 needles, 2 arms!). The electic shock was uncomfortable for those couple of seconds, but that was it. I'd say the tops of my arms ached for a couple of days, but again, no more than if i'd had the flu jab really.

Side-effects wise, i'd say it is just the soreness in the tops of the arms for a couple of days, but nothing major. They asked me to fill-in questionnaires about pain during and after. I think out of 10 I said 4 during and 2 after. Uncomfortable, but i'd take that over a bone marrow aspirate (and definately a biopsy!) any day of the week!!!

My feeling is it was something I thought was worth doing. I saw it as a minor inconvenience for me in additional appointments at Hammersmith and some uncomfortableness with the actual vaccine. My PCR was ok, but ideally would be a bit lower. I had talked with my consultant about moving to a 2nd generation, but i'm glad that I didn't at this stage as that would have excluded me from this trial, and also as I said, I don't consider myself to have any side-effects asuch from the imatinib, so am not that keen to move to an unknown (for me) 2nd gen at the moment.

The team at Hammersmith are great and provide all the information you require. As you're probably aware, you continue taking the same dose of imatinib or whatever while on the trial, and they'll analyse your blood to see if they can see any evidence of your immune system responding to the vaccine. I think the Hammersmith team mentioned they have 4 people they've done the injections for. I think they said 1 experienced a high temperature for an hour after, but that was all and it went back to normal. For the first couple of vaccines they do ask you to hang around after just in-case you experienced any side-effects, so I went to get a sandwich and hung around for an hour or two.

Hope that's useful. If you have any other questions that i've not covered, let me know. I think it's quite an exciting time and it could be this provides a kickstart to reducing the PCR and perhaps could be the start of CML management via a regular (or not so regular!) injection! I'll try and take a picture of the machine and "gun" at my next appt if anyone thinks they'd find it useful. I was planning on starting a thread on here about the WIN trial, but you've obviously beaten me to it!

Just wanted to say a big thanks to Sandy for providing this forum - it certainly helped me in the early days. Although I post very infrequently, I often browse the site!

Best wishes, Bryan.

Hi All, 

Just thought it was worth letting you know that we've just heard there are plans to run a similar "vaccine" trial for patients on nilotinib.  At Jed's appointment at HH earlier this week we met the doctor/researcher who will be running the trial, and it starts next year (2012).  

There are no firm details at this point other than the inclusion criteria are two years min taking nilotinib, measurable but residual levels of disease present, and HLA 2+ gene (which we were told most caucasians will have in their genetic make up). The only other thing we know is that it is a different vaccine to that being used on the WIN trial, i.e. not part of the tetanus family, but the idea is that it works in the same way by acting as an immune booster. 

We're expecting they will tell us more about it in a few months once they've sorted out all the paperwork that is needed for clinical trials, and I will let you know when we hear.

Although the Doc was very clear that it's way too early to be too optimistic or to pin hopes on this trial, I am certainly encouraged that the research into alternative/better treatments for CML continues.  It gives me so much hope for the future .

Happy Christmas everyone! 

Bhiru  

Hi all,

I was diagnosed in May 2010 and on imatinib by the end of that month, so not quite long enough to satisfy the 2 year criterion. I will be however before recruitment ends in July.

In my case having reached CCyR a year ago, the PCR results began at 89%, then were close to zero and have since climbed to 9% and at last count 23%.  Next week I'll have another bone marrow aspirate test with a view to starting on nilotinib.

I've recently had a mutation analysis which shows no mutation. 

I've read above that some who achieve CMR are considered to have results too good for the trial. I wonder if the converse might be true in my case?.

It would otherwise seem to be an alternative to second stage therapy.       

Thanks for the reply Sandy,

As the CML is progressing I now realise that it is not approriate as I might become increasingly ill during such a trial.

I'm to start on nilotinib in a week's time and not looking forward to finding two 3 hour slots in the day without food.

Jeff.

Sandy, Yes I mentioned the negative mutation test above. I appear to have just stopped responding. 

I'd be very happy to wake using an alarm, I don't need it since I'm usually awake before that time. One of my symptoms before diagnosis was lack of sleep due to a raised heart rate. Since treatment waking early with a raised heart rate subsided. It happens now and then, which I put down to anxiety.

It would be 3 hours fasting. 2 before and at least one after. Not too much of a problem in the morning but difficult in the evening.

It's a psychological thing I suppose.Taking imatinib was something that allowed me to put CML out of my mind, whereas it will be difficult not to pre-occupied with a schedule which makes awareness of CML central to one's life       

Jeff

Hi Chrissie,

Can you please update on the DNA Vaccine.How it went for you.

Thanks,
Lucky