Phase-I and randomized phase-II trial of panobinostat in combination with ICE (ifosfamide, carboplatin, etoposide) in relapsed or refractory classical Hodgkin lymphoma

Abstract

This phase-I/phase-II study evaluated panobinostat in combination with ifosfamide, carboplatin, etoposide (P-ICE) in relapsed/refractory classical Hodgkin lymphoma. During phase I, panobinostat was given daily on Monday/Wednesday/Friday starting one week prior to Cycle 1 (C1) of ICE and during two weeks of C1-2 of ICE (Schedule A). No DLT was observed at 30 mg. However, frequent (84%) grade-4 thrombocytopenia during second week prompted us to omit the second week of panobinostat 30 mg (Schedule B) for phase II, where this regimen was compared to ICE.

In the randomized phase-II study, CR was seen in 9/11 (82%) and 8/12 (67%) for P-ICE and ICE, respectively (p = .64). Grade-4 neutropenia (55% vs. 8%) and thrombocytopenia (100% vs. 33%) were more common in P-ICE. In summary, combination therapy using panobinostat produced high CR rate at the cost of greater bone marrow toxicity. Investigation of panobinostat with less myelosuppressive agents is of interest.

Keywords:

• Classical Hodgkin lymphoma
• panobinostat
• phase-I study
• phase-II study
• salvage chemotherapy
• histone deacetylase inhibitors

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1359741.

Additional information

Funding

This study was supported in part by Cancer Center Support (Core) Grant CA 016672 from the National Cancer Institute, National Institutes of Health, to The University of Texas MD Anderson Cancer Center, and by Research Funding from Novartis.