Results of a Phase III study of CC-486 (oral form of azacitidine) showed a significant improvement for older patients who had been transfusion dependent. The results were favorable when compared to a placebo. According to Ash Clinical News, the trial endpoints were presented at the twenty-fifth annual congress of the European Association of Hematology.
Dr. Guillermo Garcia-Manero, MD Anderson at Texas University was the lead investigator. The study involved patients aged 30 to 89 (median age 74) with low-risk MDS (myelodysplastic syndromes), transfusion-dependent anemia, and low platelet count (thrombocytopenia).
About Phase III Trial Results
The investigational drug CC-486 and the placebo together with best supportive care were administered on days one through twenty-one of a twenty-eight-day cycle.
Dr. Garcia-Manero reported that the study outcome was analyzed at the 6th cycle. Patients who became transfusion independent (30% vs. 11.1%) or had greater than fifty percent reduction in their transfusion requirements showed improvement in their platelets and red blood cells (erythroid) beginning at cycle 3. These patients found that their disease did not progress and they stopped treatment.
The patients were monitored to measure progression to acute myeloid leukemia (AML), overall survival, whether they developed secondary malignancies, or if they developed the need for other MDS therapy. Twenty-eight percent of patients being treated with CC-486 remained transfusion free for more than eighty-four days compared to patients treated with placebos (5.6%).
The patients who continued to require transfusions or did not have an adequate response when assessed at cycle 6 left the trial.
About Safety Results
Approximately thirty percent of patients who were treated with CC-486 had to discontinue treatment due to adverse events. In the placebo group that number was twenty-eight percent with both groups exhibiting grade one and two gastrointestinal symptoms.
Dr. Garcia-Manero reported that ninety percent of the subjects in the CC-486 cohort vs. seventy-three percent of those in the placebo cohort exhibited a grade three or four adverse events. The CC-486 adverse events mostly occurred in the first and second cycles.
There were more deaths during the first fifty-six days, mostly related to infection, in the CC-486 group (16) compared to six in the placebo cohort. Therefore, despite favorable results, the study was closed early at the request of the Committee for Data Safety because of the high mortality rate.
Dr. Garcia-Manero believes that an oral hypomethylating agent will eventually replace the current standard of care for MDS for which there are currently few options.
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