Cell Therapeutics, Inc. (CTI) announced it has filed for a Special Protocol Assessment (SPA) with the US Food and Drug Administration (FDA) for the design of its new phase III trial of pixantrone for patients with relapsed or refractory aggressive B-Cell non-Hodgkin's lymphoma (NHL).

In the filing, CTI proposed to the FDA that the randomized study will compare pixantrone plus rituximab against the current standard regimens used to treat this patient group. This trial is planned to enrol relapsed or refractory aggressive B-Cell NHL patients who failed first-line to third-line treatment with standard chemotherapy and are not transplant eligible.

"We anticipate the majority of the patients for this trial will be enrolled in the US," said Jack Singer, M.D., chief medical officer at CTI. "There are no approved agents in this setting and no standard of care regimens so the unmet medical need is notable. We have proposed that the major endpoints for the trial will include response rate, progression free survival, as well as overall survival."

Following the FDA's feedback on the trial design and the endpoints, CTI plans to initiate this study later in 2010.

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--forming 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 aggressive lymphoma without unacceptable rates of cardiotoxicity.

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