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

Journal Article (Journal Article;Multicenter Study)

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.

Full Text

Duke Authors

Cited Authors

  • Vogl, DT; Martin, TG; Vij, R; Hari, P; Mikhael, JR; Siegel, D; Wu, KL; Delforge, M; Gasparetto, C

Published Date

  • August 2017

Published In

Volume / Issue

  • 58 / 8

Start / End Page

  • 1872 - 1879

PubMed ID

  • 28140719

Electronic International Standard Serial Number (EISSN)

  • 1029-2403

Digital Object Identifier (DOI)

  • 10.1080/10428194.2016.1263842


  • eng

Conference Location

  • United States