Cell Therapeutics, Inc. (CTI) announced that it has initiated its randomized pivotal trial of pixantrone for the treatment of relapsed/refractory Diffuse Large B-Cell Lymphoma (DLBCL). The clinical trial is now open to patient enrollment. The 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 has received one to three prior lines of therapy.

The PIX-R trial utilizes Progression Free Survival (PFS) and Overall Survival (OS) 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.

“We are pleased to open enrollment for this study and have been in communication with leading cancer clinical sites that are enthusiastic about participating in the study largely based on the positive results of our previous study, PIX301, in relapsed/refractory aggressive non-Hodgkin's lymphoma patients,” said Jack W Singer, MD, chief medical officer of CTI. “There is an unmet medical need in this patient group, and the lack of any FDA approved drug for these patients should generate strong interest in the trial from both the patients and physicians.”

The PIX-R trial may serve as either a post-marketing commitment trial or as a follow-on pivotal trial depending on the outcome of a formal appeal that CTI submitted to the Food & Drug Administration's (the FDA) Office of New Drugs in the FDA's Centre for Drug Evaluation and Research in December 2010 regarding its 2010 decision about CTI's New Drug Application (the NDA) 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 (NHL) patients. CTI expects a decision regarding its appeal in the second quarter of 2011.

The PIX-R trial is designed to be a randomized, multi-centre study comparing pixantrone plus rituximab to gemcitabine plus rituximab in patients with relapsed or refractory DLBCL or DLBCL transformed from follicular lymphoma who have received one to three prior lines of therapy, including CHOP-R or an equivalent regimen.

The patients to be enrolled in the PIX-R trial cannot be eligible for high-dose (myeloablative) chemotherapy and stem cell transplant, but patients who relapse after such a procedure are eligible. The co-primary endpoints for the PIX-R trial are PFS and OS with secondary endpoints including Overall Response Rate (ORR) (ORR equals complete responses plus partial responses), complete response rate and safety. CTI is targeting to enroll 350 patients over 18 months in the PIX-R trial.

Pixantrone is a novel aza-anthracenedione that has distinct structural and physio-chemical properties that make its anti-tumour activity unique in this class of agents. Similar to anthracyclines, pixantrone inhibits Topo-isomerase II, but unlike anthracyclines, rather than intercalation with DNA, pixantrone alkylates DNA and forms stable DNA adducts with particular specificity for CpG rich, hyper-methylated sites. These structural differences resulted in significantly enhanced anti-lymphoma activity compared to doxorubicin in preclinical models.

In addition, the structural motifs on anthracycline-like agents that are responsible for the generation of oxygen free radicals and the formation of toxic drug-metal complexes have also been modified in pixantrone to prevent the binding of iron and perpetuation of superoxide production--both of which are the putative mechanism for anthracycline induced acute cardiotoxicity. These novel pharmacologic differences may allow re-introduction of anthracycline-like potency in the treatment of relapsed/refractory diffuse large lymphoma without unacceptable rates of cardiotoxicity.

CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable.