Imatinib ("Gleevec" / "Glivec") Finally Starts a Phase-II Clinical Trial

A year ago, researchers (Drs. Gitelman and Bluestone) at UCSF filed the paperwork to start a clinical trial testing Gleevec on people.  Now, they can finally start enrolling people in the trial.  The generic name for this drug is Imatinib.  It is sold as Gleevec in the US and Glivec in most of the world.

Gleevec is a drug already approved for treating cancer.  Patients will take a daily pill, will visit the clinic at 2 weeks, then monthly for the first year, and after that twice per year.  The researchers will measure C-peptide (to see if patients are generating their own insulin) as well as how much injected insulin the person needs, and their A1c numbers.

I've previously blogged on this trial here:
http://cureresearch4type1diabetes.blogspot.com/2013/02/possible-cures-for-type-1-in-news-mid.html

I also created a "Timeline of Gleevec as a Potential Cure for Type-1 Diabetes" that you can look at.  This timeline is experimental, so if you have any suggestions on how to make ti better, please email them to me.

They are hoping to finish collecting data in 2016 and complete the trial by 2018. It is a 66 person trial (44 will get the treatment, 22 will be in the placebo group). But this is a honeymoon trial, only people within 100 days of diagnosis will be included. Imatinib is a relatively new cancer drug, which is popular because it targets an enzyme that only cancer cells have, so it is relatively non-toxic to non-cancer cells. (The buzzword is "targeted".) The obvious question is, why would it be expected to work on type-1 diabetes?  It's not clear (at least to me) exactly why Gleevec should stop type-1 diabetes.  It does target parts of the immune system and it does lower inflammation, so either one of those (or both) could be it's mechanism of operation.  Or, it could be something completely different.  The work done in mice suggests that it might be the last option: a completely different mechanism, but there is not enough data to be sure.

Unfortunately, right now, they are only recruiting patients 18 years and older (an FDA limitation). Since this is a honeymoon trial, that is a serious limitation, and will make it hard to find people to recruit. The hope is that after some adults are successfully included in the study (and no safety issues come up), they will be able to lower the recruitment age for future patients, and fill the rest of the trial more quickly.

They are recruiting at several locations:
San Francisco: Contact: Chrinstine Torok, RN 415-502-9089 torokc@peds.ucsf.edu
Denver Contact: Jennifer Smith 303-724-8272 jennifer.e.smith@ucdenver.edu
Indianapolis Contact: Jennifer K Terrell 317-944-2584 jkramey@iu.edu
Omaha Contact: Chris Smith 402-280-4319 christosmith@live.com
Philadelphia Contact: Charles Isaacs 215-590-7222 isaacsc@email.chop.edu

Wikipedia: http://en.wikipedia.org/wiki/Imatinib
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01781975

Orange Book Entry: http://www.accessdata.fda.gov/scripts/cder/ob/docs/temptn.cfm

Joshua Levy
http://cureresearch4type1diabetes.blogspot.com 
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF, JDCA, or Tidepool news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

Possible Cures for Type-1 in the News (Mid Feburary)

Clinical Trial of Diamyd, Ibuprofen ("Advil") and Vitamin D

Diamyd (GAD65) is a protein which is one of the targets of the autoimmune attack that starts off type-1 diabetes. It was developed with the idea that giving it to people with type-1 diabetes would teach their immune systems to not attack their own beta cells. It would be like giving someone who is allergic to peanuts, just a tiny amount of the peanut protein that triggered their allergy, in the hopes that they would build up tolerance.

Unfortunately, although it worked in mice and (to some degree) in phase-II studies in people, it failed in phase-III studies in newly diagnosed type-1 diabetics.   There are still a couple of smaller on going studies.  For example, to see if Diamyd will help prevent type-1 in high risk people who have not yet been diagnosed with the disease.

So that brings us to this study. The idea behind it is:

1. Give more Diamyd vaccine than was given in the past. About twice as much.
2. The Vitamin D is supposed to stimulate the part of the immune system that reacts to the Diamyd vaccine, so it makes for a more powerful vaccination effect.
3. The Ibuprofen ("Advil") lowers the inflammation in the pancreas, which may help save beta cells, and may help the vaccine work better, and may do both.

The study will include 60 children (aged 10 to 18) in the honeymoon phase. They will be followed for 30 months, but expect some results after only 6 months. The participants will be divided into 4 groups of 15. One will be a placebo group, and the other three will each get different combinations of the three treatments.  Since they hope to start in February 2013, I think it is reasonable to expect the 6 month results in the second half of 2015 and the 30 month results by the end of 2017.  That's assuming it takes them 2 years to recruit 60 people.  I have not yet seen a clinical trials record for this, yet.

Press release: http://www.diamyd.com/docs/pressClip.aspx?section=investor&ClipID=738266

More About Diamyd

This is a full PhD thesis that was written based on data from Diamyd's phase-II clinical trial.
http://liu.diva-portal.org/smash/record.jsf?pid=diva2:562438
http://liu.diva-portal.org/smash/get/diva2:562438/FULLTEXT01

Imatinib ("Gleevec" / "Glivec") Starts a Phase-II Clinical Trial

This study has not yet started recruiting, but when it does, it will be a 66 person trial.  It is double blind and placebo controlled.   It is open to honeymooners (first 100 days), including children.  They hope to start in April 2013 and end by April 2017.  I"m not sure of the details, but I think patients will take a pill daily for the first year.  They will have clinic visits monthly for the first year, and twice a year thereafter.

Imatinib is a relatively new cancer drug, which is popular because it targets an enzyme that only cancer cells have, so it is relatively non-toxic to non-cancer cells.  (The buzzword is "targeted".)  The obvious question is why would it be expected to work on type-1 diabetes.   The work done so far in mice suggests that it is a different pathway entirely, which leads to it's effect against type-1.

Some background on why this might work (in order, earliest to most recent):
   Animal models 2007: http://www.fasebj.org/content/21/2/618.abstract
   More mice 2008: http://www.ncbi.nlm.nih.gov/pubmed?term=19015530
   Press release: http://www.ucsf.edu/news/2008/11/4166/cancer-drugs-type-1-diabetes
   Human tissue 2011: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0024831

Notice the progression, and the speed:  First tested in animals in 2007.  First tested in people in 2013.  And remember: this is for a drug that is already approved, for another disease!

Wikipedia: http://en.wikipedia.org/wiki/Imatinib
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01781975

Vitamin D Starts a Phase-II Clinical Trial

So far, there is no evidence that Vitamin D can cure or treat type-1 diabetes, and only a little evidence that it can prevent the disease.  This trial is trying to cure or treat type-1 diabetes by giving Vitamin D during the honeymoon phase.

The trial is being done in Nationwide Children's Hospital (Columbus, Ohio, USA) by Dr.Kathryn J Stephens and Dr. Robert P Hoffman.  It has not started enrollment, but they plan to enroll 54 people.  Half will get vitamin D for 9 months, half will get a placebo.  They hope to have results in March 2014.

I had previously reported on a vitamin D trial, but that was a population based trial, not an intervention trial.  This is an intervention trial, which are typically much higher quality. 

Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01724190

A Note About Terminology

I know that some people are very emotional about saying "a person who has type-1 diabetes" vs. saying "a type-1 diabetic", as in "they gave the drug to five people with type-1 diabetes" vs. "they gave the drug to five type-1 diabetics".  Some people object strongly to the second form, because they think that it defines the person by the disease; that it signals in some way that the disease is the person or the person is the disease.

Personally, I usually use the first form, because I prefer it and because I know that some people really object to the second form.  But I'm not fanatical about it, and you will occasionally see me refer to "type-1 diabetics".  I'm not trying to insult anyone when I use the second form.

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My blog contains a more complete non-conflict of interest statement.   Thanks to everyone who helps with the blog.
Clinical Trials Blog: http://cureresearch4type1diabetes.blogspot.com
Cured in Mice Blog: http://t1dcuredinmice.blogspot.com/