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Addition of Pixantrone to Rituxan Therapy Significantly Prolongs Time to Disease Progression and Improves the Overall Response Rate Compared to Rituxan Alone in Relapsed or Refractory Indolent Lymphoma

Randomized Controlled Trial Meets Primary and Secondary Endpoints

NEW YORK, NY -- November 9, 2005 -- At a presentation at the CIBC World Markets 16th Annual Healthcare Conference, Cell Therapeutics, Inc. (CTI) presented results from a randomized controlled study of Rituxan versus Rituxan plus pixantrone in 38 relapsed or refractory patients who had previously failed up to five prior treatments for indolent non-Hodgkin's lymphoma (NHL).

The study achieved its primary objective of prolonging the time before a patient's lymphoma progressed (time to disease progression, or TTP). Patients receiving the combination of Rituxan and pixantrone had an 87% overall improvement in TTP compared to Rituxan alone.

Median TTP estimate for the pixantrone/Rituxan recipients was 13.2 months compared to 8.1 months for Rituxan alone (hazard ratio 0.13, log rank P <.001). The one- and two-year progression-free survival estimates were 66% and 44% for the pixantrone/Rituxan recipients compared to zero% for the Rituxan patients for both measurement intervals (P <.001 and 0.003, respectively).

The study also met its secondary endpoint demonstrating a significant improvement in major objective responses (>/= 50% shrinkage in tumor size). Seventy-five% of patients treated with the pixantrone/Rituxan combination achieved a major response, with 35% achieving a complete response. This compares to 33% major response in patients who received Rituxan monotherapy, including 11% achieving a complete response (P =.02).

Side effects on pixantrone were generally mild (grade 1 or 2) with the exception of severe (grade 4) treatment-related neutropenia, which was seen in two patients.

The median cumulative dose of pixantrone administered was 1014 mg/m²; no cases of treatment-related grade 3 or 4 cardiac toxicity were reported.

"Obviously we are very pleased and excited by these results, which demonstrate a significant advantage of adding pixantrone to the standard of care, Rituxan, in treating indolent non-Hodgkin's lymphoma," noted Jack W. Singer, M.D. Chief Medical Officer at CTI. "Despite the small sample size, the high degree of statistical significance underscores the notable activity of pixantrone in indolent NHL."

About the Phase 3 Trial
The multi-center randomized trial, also known as PIX302, evaluated the addition of pixantrone (90 mg/m2 given on days 1 and 8 every 21 days) to standard Rituxan therapy (375 mg/m2 given on days 1, 8, 22, and 29) to Rituxan therapy alone among patients with relapsed or refractory indolent NHL.

The trial was designed, pursuant to a SPA (Special Protocol Assessment) with the FDA, to enroll a total of 728 patients in order to detect a 30% improvement in TTP between treatment arms, the primary endpoint of the study. Overall response rate was a secondary endpoint of the trial.

Patients with histologically confirmed CD20 positive NHL who had failed one or more prior treatments were included in the trial. Exclusion criteria consisted of patients who were shown to be resistant to Rituxan or who had prior stem cell or bone marrow transplants.

The study was stratified for known risk factors that may impact response and duration of response including IPI classification, number of prior regimens (1-2 versus >2), and prior anti-CD20 regimen. Patients were followed for 24 months with disease assessments made at 3-month intervals following their last day of drug therapy.

The study was closed in 2004 due to difficulty in meeting the initial enrollment target. A total of 38 patients were evaluable for response; 20 patients (median age 67 years) were randomized to the pixantrone/Rituxan arm with 18 patients (median age 59 years) on the Rituxan arm.

The pixantrone-Rituxan combination produced a complete response (CR) in seven patients (35%), with 8 patients (40%) experiencing a partial response (PR) and four patients (20%) with stable disease (SD). Rituxan monotherapy produced a CR in 2 patients (11%), PR in 4 patients (22%) with 6 patients having SD (33%).

This corresponds to a major objective response rate of 75% in the combination therapy arm compared to 33% in the Rituxan group (p=0.021). The combination of Rituxan and pixantrone was well tolerated with the only severe (grade 4) toxicity reported being neutropenia in two patients. Other toxicities were generally mild to moderate and consistent with the known safety profile for Rituxan monotherapy, except for mild (grade 1-2) cardiac side effects, fatigue, anorexia, and alopecia, which were seen only on the combination treatment arm.

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 simplify administration compared to the currently marketed anthracyclines.


SOURCE: Cell Therapeutics, Inc.

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