TY - JOUR
T1 - Phase I/II study of the novel proteasome inhibitor delanzomib (CEP-18770) for relapsed and refractory multiple myeloma
AU - Vogl, Dan T.
AU - Martin, Thomas G.
AU - Vij, Ravi
AU - Hari, Parameswaran
AU - Mikhael, Joseph R.
AU - Siegel, David
AU - Wu, Ka Lung
AU - Delforge, Michel
AU - Gasparetto, Cristina
N1 - Publisher Copyright:
© 2017 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2017/8/3
Y1 - 2017/8/3
N2 - 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.
AB - 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.
KW - CEP-18770
KW - Delanzomib
KW - phase I/II study
KW - proteasome inhibitor
KW - relapsed/refractory multiple myeloma
UR - http://www.scopus.com/inward/record.url?scp=85011266750&partnerID=8YFLogxK
U2 - 10.1080/10428194.2016.1263842
DO - 10.1080/10428194.2016.1263842
M3 - Article
C2 - 28140719
AN - SCOPUS:85011266750
SN - 1042-8194
VL - 58
SP - 1872
EP - 1879
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 8
ER -