Data from phase II study of Trisenox (arsenic trioxide) injection in myelodysplasia

Dec 5 2004

At the 46th Annual Meeting of the American Society of Hematology (ASH) preliminary data were presented from a phase II study of Trisenox (arsenic trioxide) injection in myelodysplasia (MDS).

The multicenter European study, led by Norbert Vey, M.D. of Institut Paoli-Calmettes, in patients with both higher-risk (HR) and lower-risk (LR) MDS, showed that single-agent Trisenox produced a defined hematologic response rate in all patients of 27 percent (12 of 51 LR, 19 of 64 HR), including one complete response in a higher-risk patient. Encouragingly, 31 percent of the patients with excess blast cells (22 of 71 RAEB patients, five of 11 RAEB-t patients and one of seven CMML patients) achieved a response. Cell Therapeutics, Inc. (CTI) markets Trisenox in the United States and Europe.

"We're pleased with the results of this study, which continue to provide evidence that Trisenox is active in MDS. Given this positive activity and the good safety profile, we look forward to seeing data from Trisenox in combination studies," stated Vey.

The objectives of the trial are to determine the safety and efficacy of single agent Trisenox in patients with lower-risk and higher-risk disease. Trisenox was administered at a dose of 0.3 mg/kg for five days in the first week and 0.25 mg/kg twice weekly thereafter. In addition to the 16 patients who became red blood cell transfusion independent, seven others had their red blood cell transfusion requirements reduced by more than 50 percent. There were also a total of five of 40 patients (13 percent) who became platelet transfusion independent. Most treatment-related adverse events were mild to moderate with one reported case of grade 4 neutropenia and two cases of grade 4 thrombocytopenia.

"It is potentially quite important that a high proportion of patients with higher-risk MDS responded with a hematologic improvement and a decrease in the number of blasts cells," stated Jack W. Singer, M.D. and Chief Medical Officer at CTI. "Also notable is the reduction in transfusion dependence and the durable responses we're seeing with Trisenox. In this trial, 16 of 93 patients (17 percent) who had red blood cell transfusion dependence became transfusion independent after Trisenox treatment. Major responses were seen after a median of just over one month in both higher- and lower-risk patients and the median duration of response was greater than four months. The full duration of responses is not yet known as 13 patients were still responding at the time of data release."

Trisenox (arsenic trioxide) is marketed by Cell Therapeutics, Inc.. 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.