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

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.

• Authors: Dan T Vogl, Thomas G Martin, Ravi Vij, Parameswaran Hari, Joseph R Mikhael, David Siegel, Ka Lung Wu, Michel Delforge, Cristina Gasparetto
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 58 Issue 8 Pg. 1872-1879 (08 2017) ISSN: 1029-2403 [Electronic] United States
• PMID: 28140719 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Boronic Acids
• Proteasome Inhibitors
• Threonine
• delanzomib

Topics

• Aged
• Boronic Acids (administration & dosage, adverse effects, therapeutic use)
• Drug Resistance, Neoplasm
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Multiple Myeloma (drug therapy, mortality, pathology)
• Proteasome Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Recurrence
• Retreatment
• Threonine (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Treatment Outcome