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Phase I/II study of the novel proteasome inhibitor delanzomib (CEP-18770) for relapsed and refractory multiple myeloma. Leuk Lymphoma 2017 08;58(8):1872-1879 PMID: 28140719

Pubmed ID

28140719

DOI

10.1080/10428194.2016.1263842

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/m. Dose-limiting toxicities (DLTs) at 2.4 mg/m 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.

Author List

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

Author

Parameswaran Hari MD Chief, Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-85011266750   13 Citations

MESH terms used to index this publication - Major topics in bold

Aged
Boronic Acids
Drug Resistance, Neoplasm
Female
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Multiple Myeloma
Proteasome Inhibitors
Recurrence
Retreatment
Threonine
Treatment Outcome
jenkins-FCD Prod-332 f92a19b0ec5e8e1eff783fac390ec127e367c2b5