Preliminary Phase II TRISENOX Data

Press Release Source: Cell Therapeutics, Inc.

Combination of TRISENOX(R), Vitamin C and Low-Dose Melphalan Produces 54 Percent Objective Response Rate in Late-Stage Multiple Myeloma Patients
Monday June 14, 7:02 am ET 
Preliminary Phase II TRISENOX Data Presented at International Conference

GENEVA, June 14 /PRNewswire-FirstCall/ -- At the 9th Congress of the European Hematology Association (EHA) preliminary data were presented from a multicenter, phase II study of TRISENOX® (arsenic trioxide) in a combination regimen known as MAC (melphalan, TRISENOX and vitamin C) in heavily pretreated multiple myeloma patients who had either relapsed or failed to respond to standard and/or investigational therapies. Preliminary analysis of this ongoing study, led by James Berenson, M.D. of the Institute for Myeloma & Bone Marrow Cancer Research, showed that the TRISENOX-combination produced disease responses in seven of the 13 evaluable patients (54 percent). Three additional patients achieved stable disease for an overall disease control rate of 77 percent. These patients had failed multiple prior therapies including stem cell transplant (6), bortezomib (2), thalidomide or revlimid (9) or prior melphalan (7). Cell Therapeutics, Inc. (CTI) (Nasdaq: CTIC; Nuovo Mercato) markets TRISENOX in the United States and Europe.
          
    
"The preliminary results are encouraging in this group of heavily pretreated patients who have received an average of four prior regimens (range 2-8). An important component of this study will be to determine if this combination can improve kidney impairment, a common complication in multiple myeloma patients. In our previous experience this regimen improved kidney function in five of five patients," stated Berenson. "This study uses a very low dose of melphalan supporting the preclinical evidence that TRISENOX can sensitize tumors to chemotherapy. It also provides a very effective non- steroid containing regimen which spares patients the severe, often disfiguring side effects of high-dose, steroid-containing regimens."

The objectives of the study are to determine the response rate to MAC and the time to disease progression in addition to testing the safety and tolerability of the combination. Patients receive melphalan (0.1 mg/kg) daily for the first four days of each six-week cycle. TRISENOX (0.25 mg/kg) is administered in a loading dose (daily x 4), followed by vitamin C (1 gram) on a twice weekly schedule for the next four weeks of each cycle, with a maximum of six cycles of treatment. To date, the regimen has been well tolerated with mild and reversible cytopenias and fluid retention that was relieved by diuretics and/or steroids. There are currently 25 patients on the study which will continue to accrue to a target enrollment of 60 evaluable patients.



TRISENOX® (arsenic trioxide) is marketed by Cell Therapeutics, Inc. (CTI). TRISENOX® was approved for marketing in 2000 by the U.S. Food and Drug Administration to treat patients with relapsed or refractory Acute Promyelocytic Leukemia (APL), a rare, life-threatening form of cancer of the blood. TRISENOX® was granted marketing authorization from the European Commission in March 2002. APL, one of eight subtypes of acute myeloid leukemia (AML), represents 10-15 percent of the more than 20,000 patients diagnosed with AML each year. TRISENOX® is currently being studied in more than 40 clinical trials in a variety of cancers.

U.S. marketing approval for TRISENOX® was granted based on results from a U.S. multicenter study in which 40 relapsed APL patients were treated with TRISENOX® 0.15 mg/kg until bone marrow remission or a maximum of 60 days. Thirty-four patients (85 percent) achieved CR. When the results for these 40 patients were combined with those for the 12 patients in a pilot trial, an overall response rate of 87 percent was observed.

WARNING: TRISENOX® should be administered under the supervision of a physician who is experienced in the management of patients with acute leukemia. Some patients with acute promyelocytic leukemia (APL) treated with TRISENOX® have experienced APL differentiation syndrome -- with symptoms similar to retinoic acid-acute promyelocytic leukemia (RA-APL) syndrome. Arsenic trioxide can cause QT prolongation (which can lead to torsade de pointes) and complete atrioventricular block.

The most common adverse events associated with TRISENOX® have been generally manageable, reversible and usually did not require interruption of therapy. These have included hypokalemia, hypermagnesemia, hyperglycemia and thrombocytopenia as reported in 13 percent of the patients (n=40). Abdominal pain, dyspnea, hypoxia, bone pain and neutropenia were reported in 10 percent of these patients, while arthralgia, febrile neutropenia and disseminated intravascular coagulation were reported in eight percent of patients.