Best Promising Drug Association With Azacitidine in Higher Risk Myelodysplastic Syndromes

Summary

In order to improve the overall survival benefit observed with AZA in higher risk MDS, its combination with other active drugs in MDS must be tested. Among drugs that have demonstrated to be active as a single agent in MDS and have preclinical potential additive or synergistic activity with AZA are Histone deacetylase (HDAC) inhibitors including Valproic acid, Lenalidomide and idarubicin. Phase I studies have already been conducted or are being conducted combining those agents to demethylating agents, showing a low toxicity profile and significant responses in high risk MDS. In this phase II randomized trial, we want to identify the most promising combination of Azacitidine and another drug (among 3 drugs: Valproic acid, Lenalidomide and Idarubicin) in higher risk MDS, by comparison to Azacitidine alone. Of note, based on efficacy and toxicity, one or several combinations may be stopped, and others, previously tested in phase I trials, included after protocol amendment.

Timeline

Start

2011-06

Primary completion

2018-07

Completion

2019-06

Publications

• Jacob L, Uvarova M, Boulet S, Begaj I, Chevret S. Evaluation of a multi-arm multi-stage Bayesian design for phase II drug selection trials - an example in hemato-oncology. BMC Med Res Methodol. 2016 Jun 2;16:67. doi: 10.1186/s12874-016-0166-7.

Drugs

Indications