Phase I/II study of the novel proteasome inhibitor delanzomib (CEP-18770) for relapsed and refractory multiple myeloma

Dan T. Vogl, Thomas G. Martin, Ravi Vij, Parameswaran Hari, Joseph R Mikhael, David Siegel, Ka Lung Wu, Michel Delforge, Cristina Gasparetto

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Delanzomib (CEP-18770), a reversible P2 threonine boronic acid proteasome (β5/β1 subunits) inhibitor that showed promising anti-myeloma effects in preclinical studies, was investigated in a single-agent multicenter phase I/II study in patients with relapsed/refractory myeloma. Sixty-one patients (17 during dose escalation; 44 in the expansion cohort) received delanzomib on days 1, 8, and 15 in 28-d cycles; 47 received the maximum tolerated dose (MTD), 2.1 mg/m2. Dose-limiting toxicities (DLTs) at 2.4 mg/m2 were rash and thrombocytopenia. At the MTD, the most prominent adverse events were nausea, vomiting, anorexia, fatigue, and pyrexia; grade 3/4 thrombocytopenia and neutropenia occurred in 53 and 23% of patients, respectively. Peripheral neuropathy (21%) was limited to grades 1/2. At the MTD, 26 patients (55%) had stable disease and four (9%) had a partial response (PR). Median time to progression (TTP) was 2.5 months across the cohort. Based upon the efficacy results, development of delanzomib for myeloma was discontinued.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalLeukemia and Lymphoma
DOIs
StateAccepted/In press - Jan 30 2017

Keywords

  • CEP-18770
  • Delanzomib
  • phase I/II study
  • proteasome inhibitor
  • relapsed/refractory multiple myeloma

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Phase I/II study of the novel proteasome inhibitor delanzomib (CEP-18770) for relapsed and refractory multiple myeloma'. Together they form a unique fingerprint.

  • Cite this

    Vogl, D. T., Martin, T. G., Vij, R., Hari, P., Mikhael, J. R., Siegel, D., Wu, K. L., Delforge, M., & Gasparetto, C. (Accepted/In press). Phase I/II study of the novel proteasome inhibitor delanzomib (CEP-18770) for relapsed and refractory multiple myeloma. Leukemia and Lymphoma, 1-11. https://doi.org/10.1080/10428194.2016.1263842