This is a study for adult patients with CLL who have a specific phenotype called mutated IGVH. We know that chemoimmunotherapy for patients with CLL has been the standard of care, such as FCR, and this is a new version of FCR where we have changed some of the components of FCR including we have added ibrutinib, which stands for I, fludarabine and cyclophosphamide are the same and we have replaced rituximab with GA101, or obinutuzumab, and at the same time we have cut down the chemotherapy for three cycles. So that’s the new regimen, we call it the IFCG regimen.
When it comes to practice how is this going?
So far it’s a phase II clinical trial, we have treated 36 patients so far on this trial of which 32 patients have completed three months of therapy. What we are seeing is that the MRD negative responses in the bone marrow are what we are reporting as 87% which compares favourably to 26% with our previous regimen, with FCR, after three months. At the same time we are also seeing a high rate of complete remission rate and what we are envisioning in this trial is that patients receive a total of one year of therapy although the chemotherapy part is only for three months, after that patients continue ibrutinib and obinutuzumab for a variable duration depending on the MRD status. At the one year time-point if they are MRD negative patients are able to stop ibrutinib. So far what we are seeing is that we are able to deliver this therapy, achieve a high rate of complete remission, high rate of MRD negative remission and then they are able to stop all therapy at the one year time-point. After that we are able to follow the patients to see if they relapse or recur and so far none of the patients have relapsed or had recurrence of their disease by MRD at a median of 5.5 months of follow-up.
Can I just double-check the numbers of patients involved in this trial?
36 patients have enrolled in the study so far, our plan is to enrol a total of 45 patients.
When it came to the adverse events related to this regimen, anything in the grade 3s and 4s?
Because ibrutinib and obinutuzumab, the two new additions to this regimen, both can cause neutropenia, fludarabine, cyclophosphamide can also cause neutropenia, what we saw was that there was a 68% grade 3 or 4 neutropenia rate in the study which is higher than what we have previously reported with the use of FCR. We are not using prophylactic growth factor support for this study in the early part of the study; now that we have seen this increased neutropenia risk we have mandated the use of growth factor support such as Neupogen or Neulasta. Since that institution a few months ago the risk of neutropenia has substantially gone down. We do see a risk of atrial fibrillation, which was in approximately 10% of the patients, which is a side effect which is well-known in this trial with the use of ibrutinib. That was seen in four patients out of 36 but other than that we are not seeing any increased toxicities with this regimen.
One patient developed a cardiac toxicity?
One patient was a young gentleman, 26 years old, who had new onset congestive heart failure on the study around nine months into treatment. The patient had just started taking a couple of days before he developed the heart failure a new kind of weight loss supplement and he had actually reached out to us saying that since he started the health supplement, weight loss supplement, he doesn’t feel right and he feels his heart is pounding. Then subsequently unfortunately he passed away in the next few weeks from worsening congestive heart failure. Certainly this could be ibrutinib related because ibrutinib has been associated with some cardiac arrhythmias and rare anecdotal cases of congestive heart failure but our suspicion at this time was that given the temporal association with the use of this new medication it could be attributed to that. But that’s the only death on the study and obviously a somewhat unexplained congestive heart failure.
When it comes forward to expanding you said up to 45 patients.
Currently the study is designed for 45 patients, we have enrolled 36 patients. We expect that in the next three or four months we will fully accrue the study. We are discussing about expanding the study with more numbers of patients because we think that this is a very effective regimen for our patients and those discussions are in progress right now.