A Phase II Exploratory Study of PXD-101 (Belinostat) Followed by Zevalin in Patients with Relapsed Aggressive High-Risk Lymphoma

Soham D. Puvvada, José M. Guillén-Rodríguez, Xavier I. Rivera, Kara Heard, Lora Inclan, Monika Schmelz, Jonathan H. Schatz, Daniel O. Persky

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Objective: Aggressive lymphomas (aNHL) including diffuse large B-cell lymphoma (DLBCL) have poor outcomes in relapsed refractory patients. Prior studies have demonstrated that loss of major histocompatibility complex class II (MHCII) expression in DLBCL is associated with poor survival. The objective of this single-arm phase II study was to evaluate if PXD-101 would increase MHCII expression, synergize with Zevalin, and improve clinical outcomes. Methods: This was a single-center open-label phase II trial (NCT01686165) geared toward heavily pretreated patients with CD20-positive aNHL. The primary endpoint was overall response rate (ORR) in aNHL patients treated with 2 cycles of PXD-101 followed by restaging CT and 1 cycle of Zevalin. Results: Five patients were enrolled, and all were heavily pretreated. Therapy was well tolerated, with nausea and vomiting being the most frequent adverse events. All patients progressed after receiving therapy; the study did not achieve the required ORR to proceed to the next stage. Conclusion: The pleotropic effects of histone deacetylase inhibition and lack of clinical biomarkers have precluded a priori identification of responding patients. Thus, while we report a negative trial of PXD-101 in combination with Zevalin, this study highlights the importance of a clinically feasible biomarker.

Original languageEnglish (US)
Pages (from-to)401-405
Number of pages5
JournalOncology (Switzerland)
Volume93
Issue number6
DOIs
StatePublished - Dec 1 2017

Keywords

  • Diffuse large B-cell lymphoma
  • Non-Hodgkin's lymphoma
  • Phase II study

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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