First randomised controlled trial using FDA's SPA

The US Food and Drug Administration has provided Seattle-based Cell Therapeutics with guidance through the Special Protocol Assessment(SPA) process for a randomised pivotal trial of Pixantrone in the treatment of relapsed, aggressive non-Hodgkin's lymphoma (NHL).

The trial protocol and supporting data are in the final stages of review with the FDA and initiation of the pivotal study is planned for late March 2004. The trial is designed to examine the complete response (CR) rate, time to tumour progression, and overall survival of patients with aggressive NHL who have failed front-line and at least one second-line multi-agent chemotherapy regimen.

Patients will be randomised to receive either Pixantrone or another currently used, single-agent drug of physician's choice. FDA has indicated that Pixantrone would qualify for accelerated approval based upon the successful conclusion of this trial and supporting data from ongoing and completed clinical studies. The trial is expected to enroll approximately 320 patients with enrollment taking approximately 12 months to complete.

'Current single-agent treatments for patients who have failed two or more prior multi-agent regimens produce partial responses in only about 10-15% of patients and those responses are typically short-lived, lasting on average approximately three months. Complete responses are not typically reported in this population of patients with currently available single-agents and are considered by international lymphoma experts and the FDA as the 'gold standard' to demonstrate a clinically meaningful benefit to patients with this disease,' stated Dr James Bianco, president and ceo of CTI. 'Although anthracyclines are the most potent class of drugs for treating this disease, the cumulative heart damage associated with their use in front-line regimens prevents patients from receiving further treatment with these drugs, leaving them with no approved effective treatment options.'

The design for this pivotal trial was supported by phase I/II data from approximately 170 patients with relapsed or refractory, aggressive NHL treated with Pixantrone.

With the initiation of this pivotal study, CTI has two phase III and five phase II clinical studies of Pixantrone planned or ongoing involving single-agent or combination therapy in the treatment of first, second, or third-line aggressive NHL or indolent NHL. In the US, it is estimated that more than 33,000 patients receive salvage therapy for third-line or greater NHL each year, with more than 60,000 patients receiving multi-agent chemotherapy for front-line or second-line treatment.

Special protocol assessment process

The special protocol assessment process provides a forum for FDA and the sponsor to reach agreement as to the design, execution, and analyses proposed in protocols reviewed under this process. In general, these assessments are considered binding on the review division as well as the sponsor, unless public health concerns unrecognised at the time of a protocol assessment become evident or other scientific concerns arise.

About Pixantrone

Pixantrone is an investigational agent under development for the potential treatment of various hematological malignancies, solid tumors and immunological disorders. It was developed to improve the activity and safety of the anthracycline family of anti-cancer agents. Anthracyclines have been shown to be very active clinically in a number of tumor types. However, they are usually associated with cumulative heart damage that prevents them from being used in a large proportion of patients. Pixantrone has been designed to reduce the potential for these severe cardiotoxicities, as well as to potentially increase activity and simplified administration compared to the currently marketed anthracyclines.