A Randomized Phase Ii Study Of Azacitidine (Aza) Alone Or With Lenalidomide (Lf:N), Valproic Acid (Vpa) Or Idarubicin (Ida) In Higher-Risk Mds: Gfm'S 'Pick A Winner' Trial

Background:AZA improves overall survival (OS) in higher risk MDS, but only 50-60% of the patients respond, and median OS with AZA is only 20-24 months. As OS improvement is obtained at modest response rates, OS rather than response should probably remain the primary endpoint for all combinations with AZA, requiring large phase III trials with significant follow up. On the other hand, combinations that do not increase response will likely not improve OS. We therefore tested, based on a “pick the winner” approach, AZA combinations with the HDAC inhibitor VPA, LEN or IDA to identify, based on response, the most promising combination with AZA in higher risk MDS, that could be subsequently compared with AZA alone in a larger phase III study.