The MDS Beacon™

Intravenous Clolar (clofarabine) shows activity in higher-risk myelodysplastic syndromes (MDS), found a Phase 2 clinical trial presented June 7 at the American Society of Clinical Oncology’s (ASCO) 2010 Annual Meeting. Out of 58 trial participants with various subtypes of MDS, 36 percent responded to intravenous Clolar, reaching either complete response or improved blood cell counts, known as hematological improvement.

“Clolar’s activity does not seem to be dose-dependent,” said Dr. Elias Jabbour from the M.D. Anderson Cancer Center.

Clolar is currently approved in the United States for children with acute lymphoblastic leukemia who have relapsed or have not responded to other treatment. However, several recent Phase 1 and Phase 2 studies have demonstrated Clolar may be effective against MDS, as well (see related Beacon news).

In the current study, the trial participants received either 15 mg/m² Clolar (37 patients) or 30 mg/m² Clolar (21 patients) intravenously for five days every four to six weeks. Seventy-four percent of the participants had higher risk MDS and 60 percent had relapsed or had not responded to Vidaza (azacitidine), Dacogen (decitabine), or both. Their median age was 68 years.

Among the participants who responded to the Clolar treatment, 26 percent achieved a complete response and 10 percent had improved blood cell counts. “The low-dose schedule was better performing”, said Dr. Jabbour. Fourty-one percent of patients on the low-dose schedule responded to treatment compared to 29 percent on the high-dose schedule.

All of the responding patients reached a response within three cycles of treatment, the median cycle to response was one.

The median duration of response was 8.8 months, and the median overall survival was 7.4 months. For patients who responded to treatment the median overall survival was 13.4 months and 21.7 months for those who had achieved a complete remission. The one year overall survival was very similar in both treatment groups.

The most common side effects were nausea, vomiting, rash, and signs of liver damage. Severe side effects were rare. However, six study participants experienced liver failure. Twenty-six patients experienced infections, and infections were more common in those receiving the higher dose of Clolar, 30 mg/m².

“Better outcomes may be achieved at the lower-dose schedule with fewer treatment-related complications,” concluded Dr. Jabbour.

Dr. Jabbour suggested further trials examine lower doses of Clolar to help reduce side effects. He also recommended studying a combination of Clolar and Vidaza or Dagocen.

For more information on the results presented at ASCO, please see abstract 6504 on the ASCO Meeting website.