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.

A Phase 3 Study of Ibrutinib Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (RESONATE™)

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.