Cell Therapeutics, Inc. has announced the final clinical trial design of a randomized pivotal trial of pixantrone for the treatment of diffuse large B-cell lymphoma following discussions with the U.S. Food and Drug Administration's Division of Hematologic Products.
The new clinical trial, referred to as the PIX-R or PIX 306 trial, will compare a combination of pixantrone plus rituximab to a combination of gemcitabine plus rituximab in patients with relapsed or refractory DLBCL who have received one to three prior lines of therapy, utilizing progression free survival and Overall Survival as co-primary endpoints of the study.
The PIX-R trial, is targeting to enroll approximately 350 patients over 18 months and will include patients who have failed at least one line of previous therapy and patients who are not candidates for myeloablative chemotherapy and stem cell transplant.
During its discussions with the DHP the Company was advised that only OS would be acceptable for a formal Special Protocol Assessment agreement, however the DHP noted that the Company could conduct a study utilizing PFS along with OS as co-primary endpoints which would be an acceptable design outside of the formal SPA process. Regulatory acceptability will depend on the magnitude of the difference between the trial study arms as well as a risk and benefit analysis.
"CTI has worked with the DHP since August on an appropriate clinical trial design that may serve as either a post-marketing commitment trial or as a follow-on pivotal trial depending on the outcome of an appeal of CTI's new drug application for pixantrone based on the PIX 301 trial at the FDA's Office of New Drugs," stated James A. Bianco, M.D., CEO of Cell Therapeutics.
"We believe that pre-clinical data and results from a randomized clinical trial have already demonstrated synergy exists between pixantrone and rituximab when they are used in combination. We believe that pixantrone administered as a single agent had a significant effect on prolonging PFS with an accompanying trend in OS in the PIX 301 trial. Given these results and the similar patient population in the PIX-R trial, including the choice of comparator regimen, we believe this trial has the potential to establish the clinical benefit of pixantrone in this patient group to fulfill an important unmet medical need," added Dr. Bianco.
In December 2010, CTI submitted a formal appeal to the FDA's Office of New Drugs in the FDA's Center for Drug Evaluation and Research regarding its 2010 decision about CTI's new drug application for pixantrone. The NDA for pixantrone was based on the results of the PIX 301 trial, a randomized trial comparing pixantrone as monotherapy to a choice of standard single-agent chemotherapy in relapsed/refractory aggressive non-Hodgkin's lymphoma patients.
CTI recently met with the OND to discuss the appeal. The OND requested, and CTI plans to supply the FDA with, additional analyses from the PIX 301 trial. CTI expects a decision regarding its appeal early in the second quarter of 2011.
In Europe, the Marketing Authorization Application for pixantrone as monotherapy for patients with relapsed or refractory aggressive NHL is currently under review by the European Medicines Agency based on the pixantrone (PIX 301) phase III study results.