Tuesday, April 17, 2012

New Clinical Trial for Ibrutinib (PCI-32765): Exclusion Criteria and More

The phase 3 pivotal trial to get ibrutinib (PCI-32765) approved by the FDA is gearing up.


This is big news.

Let me get personal first.

My prior failed transplant would have knocked me out of any chance at the drug in this and maybe any other trials until approval.

Please read the exclusion criteria for this critical study listed below.

Exclusion Criteria:

  • Known CNS lymphoma or leukemia.
  • No documentation of cytogenetic and/or FISH results reflecting 17p del status in patient records prior to first dose of study drug.
  • Any history of Richter's transformation or prolymphocytic leukemia.
  • Uncontrolled Autoimmune Hemolytic Anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP).
  • Prior exposure to ofatumumab or to ibrutinib.
  • Prior autologous/allogeneic transplant
  • History of prior malignancy, with the exception of certain skin cancers and malignancies treated with curative intent and with no evidence of active disease for more than 3 years.
  • Serologic status reflecting active hepatitis B or C infection.
  • Unable to swallow capsules or disease significantly affecting gastrointestinal function.
  • Uncontrolled active systemic fungal, bacterial, viral, or other infection.
  • History of stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug.
  • Requires anticoagulation with warfarin.

Exclusion Criteria: Prior autologous/allogeneic transplant

I would be out of luck and running low on options, but instead I am so fortunate because I am here at OSU, four weeks away from my first dose of ibrutinib.

I saw that one coming, and so jumped at this opportunity here in Columbus. One of my more prescient moves.

Transplants cuts off many options, especially clinical trials, so if ibrutinib doesn't work for me, then my path is narrowed and obscured.

Exclusion Criteria: Prior exposure to ofatumumab or to ibrutinib.

Please note that any prior ofatumumab also excludes you.

Exclusion Criteria: No documentation of cytogenetic and/or FISH results reflecting 17p del status in patient records prior to first dose of study drug.

The 17p deletion exclusion seems to be a double negative.

The way I am reading it, it seems to say that unless you are 17p deleted, you CAN NOT enter the trial.

If so, that was not a turn I expected. I thought Pharmacyclics (PCYC) would go after the much larger population (market) of all new and old patients with CLL not just those with "Relapsed or Refractory Chronic Lymphocytic Leukemia".

It certainly suggests a great degree of confidence in the drug to handle the nastiest 17p del cohort. The company is betting are betting the farm on that wildest and most dangerous horse and the one most in need of taming. And maybe secretly hoping for the same wide off label use that is seen with rituximab helping to generating seven billion US dollars in annual sales.

I hear the results out the NIH trial on 17p del patients, though very preliminary, are very promising on that tough group.

Exclusion Criteria:
  • History of stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug.
  • Requires anticoagulation with warfarin.

The exclusion of those on coumadin and with bleeding in the brain is because of the history of brain hemorrhages (some fatal) that occurred in earlier phase trials. Frankly I am surprised it is not all blood thinners and anyone with a bleeding tendency similar to the exclusion in the MDACC trial with rituximab.

This important phase 3 trial NCT01578707 should be much larger to get the more statistically significant result to gain FDA approval, so there will be many more opportunities to get the drug. Take a look at the trial link, move fast if you qualify and need therapy, and watch for other similar trials if you are interested in what I believe is the best of the new bunch of small molecules.

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6 Comments:

Blogger maronedp said...

Brian,

I think the language suggests the opposite. "No documentation of 17p deletion on Fish/Flow" since it is a comparative arm, I doubt oftamumab would be a wise choice really for anyone, much less a 17p deleted patient.

By the way, I'm in the Ibrutinib trial at NIH (I have a p53 mutation) and I've responded very well thus far. After two weeks, I had a 15% reduction from 20% to just under 5% CLL cells in my bone marrow. Platelets rose to the 150's from the low 100's. It's like taking a multi-vitamin every day. Good luck with it.

April 19, 2012 at 6:06 AM  
Anonymous Anonymous said...

Funny, I read the 17p del exclusion just opposite of your reading so I sent an email query to the contact listed in the trial web page. Here is the reply.

"Thanks for your inquiry. I understand how this might be confusing.

For patients to participate in this trial, DOCUMENTATION of 17p deletion status is required.

Another way to put this is: It is required that the subject's 17p deletion status be DOCUMENTED prior to enrollment. If their status is unknown, they are excluded from the trial.

We are NOT restricting enrollment based on the presence or absence of 17p deletion.

Hope that helps. If not, please let me know. Thanks again for your inquiry.
Susan

Susan E. King, RN, MS, OCN
Medical Science Liaison
Pharmacyclics, Inc.
858-603-2299"

Regards, TomD

April 19, 2012 at 6:28 AM  
Anonymous jcleri@aol.com said...

In other words.....if you are not in good health and have not had any treatments....than why on earth would you want to do a trial. Kinda seems like they would want the ones who have had no luck at the other stuff...... but then who am I. Praying that you get in and as always that there is 100% cure rate.

Greetings from beautiful Hilo Hawaii.

Judy

April 19, 2012 at 12:13 PM  
Anonymous Anonymous said...

I checked with Pharmacyclics and there is no necessity for 17p deletion .. only, that if one says they have it, there must be "documentation". So .. said another way, the trial is available for both 17p deleted and non-deleted.

April 19, 2012 at 3:32 PM  
OpenID tutihushi said...

The exclusion criteria are vague. I have asked if the exposure to ofatumumab excludes from both arms or from Ofatumumab arm f the study only... Waiting for the reply

Greg

May 7, 2012 at 5:16 PM  
Anonymous Anonymous said...

Brian,

Go for it. I am in 20th month of PCI-32765 continuous treatment and feel great. All indicators are good. Would be scuffling for life and/or going for transplant otherwise - unmutated.

May 7, 2012 at 8:34 PM  

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