Ibrutinib Versus Ofatumumab
The buzz word these days is ibrutinib because of the dramatic results of Phase I and II clinical trials recently presented at ASH. It is being put up to a final test before being considered for approval by the FDA and international government agencies for the treatment of CLL.
CLL patients are currently enrolling in a Phase III clinical trial comparing ibrutinib to ofatumumab, a monoclonal antibody already approved for the treatment of CLL. The study, known as the RESONATE study, is open to patients who have relapsed or who have refractory CLL, including those with 17p- which is considered a poor prognostic marker.
Ibrutinib blocks the Bruton's tyrosine kinase (Btk) protein which is found on healthy B-cells and CLL cells. Btk functions normally in healthy B-cells, but not in CLL cells. It is part of a signaling pathway needed by CLL cells for growth and survival. Btk also helps keep CLL cells in the lymph nodes where they are better protected.
Blocking Btk liberates the CLL cells into the blood stream
where they slowly starve and are more susceptible to treatment. As a result, patients experience a significant reduction in lymph node size, and at the same time their white blood cell count spikes but eventually normalizes as the CLL cells die.
Ofatumumab targets CD20 which is a molecule found on the surface of B-cells, including CLL cells. It was approved in 2010 for the treatment of CLL. Both ofatumumab and rituximab, another monoclonal antibody, target the CD20 molecule. Ofatumumab seems to be better at binding to CD20 than rituximab in CLL cells. It is also effective in patients who did not benefit from treatment with rituximab, making it a good comparator to ibrutinib.
The primary goal of this Phase III trial is to see if there is a clinically significant improvement in progression-free survival when ibrutinib is compared to ofatumumab, an approved treatment option. It must be shown through trial results that ibrutinib is equally effective with fewer side effects or superior to standard therapy. These results will be used by the FDA when considering the approval of ibrutinib; FDA approval would make the treatment more widely available to CLL patients.
The trial is currently open at more than 50 locations around the world and is accruing rapidly. It is a randomized trial which means the patient, the doctor and the drug company cannot choose which patient will go on which drug. To eliminate bias, a computer decides whether patients will go on the ibrutinib or ofatumumab arm. Randomized trials help demonstrate that a particular agent or regimen is beneficial on average to a large population of patients.
Additional ibrutinib trials are ongoing and others are planned. Ibrutinib has been beneficial for patients regardless of prognostic markers. One new study will specifically target patients with 17p- which are often difficult to treat. Other trials will combine ibrutinib with additional therapies for patients with relapsed or refractory CLL and there is also a trial planned comparing ibrutinib with chlorambucil as frontline therapy in elderly patients.
Phase III trial results will be reviewed by the FDA to make sure the treatment is safe and effective for use by all patients. If approved, ibrutinib will be available for CLL patients at doctors' offices worldwide. We will continue to provide updates on this Phase III trial and others as they become available.
Click here to read additional information about the trial from clinicaltrials.gov.
As with any study, enrollment is limited and a patient must meet eligibility criteria. Consult with your physician to determine if a clinical trial is an appropriate avenue for treatment.