Any info about Sirolimus trials?

[Hawaii Bill]

I am considering trying the Sirolimus/Cyclosporin clinical trial currently being held.

I was treated with ATG/Cyclo in December 2006 and had a great response for a few months, then my marrow began to lose cellularity again. It is now at 10%, but I am hanging in there with 2 units of red blood every 2 months.

I would like to participate in a trial because I want to contribute to others with this disease, now and in the future.

My readings of this and other forums reveals that there has been little success with Sirolimus (anecdotally), so I am wondering if this is the best trial for me. After all, the ATG was successful the first time, and my doc and I are pretty convinced that the Cyclo taper was too fast, and that my need to take Diltiazem for a cardiac rythym problem, which has since been fixed (yay!). We all know that the ATG is pretty harsh, so my doc thinks that I have the luxury of time to do a trial with something less harsh.

The other problem with this trial is that I will have to make 10 roundtrips from Hawaii to LA to participate (unless they cut me some slack on this!).

Anybody have any feedback or suggestions? TIA

[Wayne O'Shana]

Hi Hawaii Bill:

I did a search on Google for Sirolimus and found 583,000 hits. Reading just the first four entries made me decide that I wouldn't touch that stuff with a thirteen-foot pole. There could be a 1% chance that the people running the trial might really know what they are doing but, even if that were the case, I would advise extreme caution.

Some of our members have posted about another site: www.aplasticcentral.com

When I logged on I was amazed to discover that AA is an autoimmune disease. The first thing to do after being so amazed is to go to Google and search for "autoimmune aplastic anemia". (219,000 hits) There must be something out there that will reprogram the immune system to recognize "self" and also be able to find stuff that tends to get past the normal system.

There was a trial at UCSF for an immune system reprogramer that was aimed against multiple sclerosis, another autoimmune disease. I think the trial is over and I am eager to see the final report. If this drug works for MS it might work for dozens of other autoimmune diseases like, you know, AA.

Maybe your doc could get an early copy of the final report.

Best wishes ---

[Hawaii Bill]

Hi Wayne,

Thanks for your reply!

Yes, I've also Googled just about every one of the drugs I've been given. None of them are very "safe", but it seems to be a matter of choosing between the lesser of two evils, sometimes. I don't mind taking the risk, but I want it to be with something that has the best chance of working.

I am having serious reservations about this trial, and now the trial with Daclizumab seems to be more promising. I will ask Dr Paquette about it. He will have to do a major selling job to keep me interested in Sirolimus.

Given my strong response to the regular treatment, and the probability that it was just too fast a Cyclo taper, I think that I may just go that route again.

Decisions, decisions....

Bill

[Wendy Beltrami]

Hi Bill-
Just FYI, our son tried Daclizumab and it was a breeze. It didn't work but it was a breeze. Absolutely ZERO negative side effects. It has worked for some so I would say go for it!

Wendy/mom to Grant age 16.5
dx 12/4/98 AA

[michelle_lapuz]

Instead of Cyclosporin post ATG I was given Tacrolimus (similar to Sirolimus) with absolutely no side effects but also absolutely no remission....more side effects from the prophylaxis drugs associated with post-ATG treatment.

Good luck with whatever you choose

Michelle

[Hawaii Bill]

Originally Posted by Wendy Beltrami

Hi Bill-
Just FYI, our son tried Daclizumab and it was a breeze. It didn't work but it was a breeze. Absolutely ZERO negative side effects. It has worked for some so I would say go for it!

Wendy/mom to Grant age 16.5
dx 12/4/98 AA

Thank you for letting me know that it has worked for some, although it's too bad that it did not work for Grant. That is more encouraging that what I've read about Sirolimus.

I'm really excited about meeting Dr Paquette and hearing what he has to say.

Bill

[Hawaii Bill]

Originally Posted by michelle_lapuz

Instead of Cyclosporin post ATG I was given Tacrolimus (similar to Sirolimus) with absolutely no side effects but also absolutely no remission....more side effects from the prophylaxis drugs associated with post-ATG treatment.

Good luck with whatever you choose

Michelle

Thank you.

[Lisa V]

Aloha Bill,

I don't have any experience with Sirolimus, but just from what I could pick up from a quick search I didn't see anything about it that was any scarier than for other immunosuppressants, including cyclosporine. Did I miss something? In fact the advantage seems to be that it would be much easier on your kidneys, which is something my husband has to constantly battle with the cyclo.

On the other hand, ATG/cyclo has a proven track record that is better than any other IST protocol for AA, at least so far. The fact that you responded the first time would tend to lean me in that direction, that and the 10 trips to LA! Who pays for that, does the trial cover all travel and lodging costs? Still humbug!

How quickly did you do the taper? Ken also relapsed from a too-quick taper, but a second ATG turned it around for him. That was in Feb. '06. He's still taking cyclo and it's possible now he'll have to remain on it indefinitely, but he's transfusion-free, stable, feels fine, and his counts continue to improve gradually. Much as I would like to see clinical trials done on anything that might help give his kidneys a break, I'm not sure this trial is the best thing for you at this point.

[Hawaii Bill]

Thanks for sharing your thoughts, Lisa.

Yep, everything you said has crossed my mind.

The Sirolimus trial seems like a no-go for me right now, but I will reserve the final decision until after I see Dr Paquette. There are other trials that might be a better fit, too.

Since this is such a rare disease, and it needs research, I feel that it would be good to try something different for the good of others. But there is also a limit to that.

The taper I did was most likely too fast, even my doctor said that he might have jumped the gun due to my incredibly good BMB biopsy results 3 months after the IST. I was only too glad to cut back on that stuff, but the second time around, I will be happy to keep taking it for as long as it takes.

I understand the Europeans do a slower taper as a rule, and the stats I saw show a lesser relapse rate.... but I certainly don't have all the info....

I'm SO glad to hear your husband is doing so well!!!!! Here's to more of the same for him (and you!). Good luck!!!!

[Hawaii Bill]

Just wanted to update everyone:

Dr Paquette wants to try treating my relapse with a higher dose of Cyclosporin alone, to see if I respond. I had not even thought of that solution, out of all the possibilities (guess that's why HE's the doctor!), but it makes perfect sense to me.

So no ATG/Sirolimus for me, at least for now.

[Hawaii Bill]

Hello!

Although it took longer than my hemo said he would expect it to, the treatment that Dr Paquette suggested back in June appears to be working!

In June, Dr P suggested a dosage of 200mg of CsA, twice a day, as a means to perhaps recover the benefits from my first round of ATG back in Dec 2006.

Since I began the new treatment, my counts have stopped their usual slow decline and have stabilized. My last PRBC transfusion was almost six months ago! It's still too early to tell if the counts will now start rising, but my platelets jumped out of the 20's and up to 35, and since the platelets were the first to respond after ATG, I am hoping that this is a similar trend.

Cheers to Dr Paquette!!!!

[Neil Cuadra]

That's great news, Bill. You and your doctors have been making the right moves and your patience has been paying off. Nobody wants to be on more cyclosporine than necessary or for longer than necessary, but it can sure make a difference when it's working. Good luck getting your other counts up!