Phase 1 study of belinostat (PXD-101) and bortezomib (Velcade, PS-341) in patients with relapsed or refractory acute leukemia and myelodysplastic syndrome

Abstract

We report the results of a phase 1 dose-escalation study of belinostat and bortezomib in adult patients with acute leukemia or MDS or CML with blast crisis. Thirty-eight patients received IV belinostat days 1-5 and 8-12 with IV bortezomib days 1, 4, 8, and 11 every 21 days. QTc prolongation was the only identified DLT. The RP2Ds were 1.3 mg/m² bortezomib and 1000 mg/m² belinostat. One patient with highly refractory MLL-ENL rearranged biphenotypic AML with multiple karyotypic aberrations had a complete pathologic and karyotypic response. One patient with post-MPN AML remained on study with stable disease (SD) for 32 cycles. Whole-exome sequencing revealed no aberrations in the first patient and a hyper-mutator genotype in the second. Eighteen patients had a best response of SD. We conclude that this treatment strategy is feasible but has limited activity in this population. Nevertheless, the factors that predict exceptional responses to this strategy warrant further investigation.

Keywords:

• Acute leukemia
• belinostat
• bortezomib
• myelodysplastic syndrome
• phase 1 clinical trial

Disclosure statement

No potential conflicts of interest were disclosed by any of the authors.

Additional information

Funding

The study was supported by grants from the National Institutes of Health (NCI RC2 CA148431, NCI P30 CA016059 [Cancer Center Support Grant to Massey Cancer Center; supported in part the Biostatistics Shared Resource], UL1TR002649 [CTSA award from the National Center for Advancing Translational Sciences to the VCU C. Kenneth and Dianne Wright Center for Clinical and Translational Research]), and through funding from Millennium-Spectrum.