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Leuk Lymphoma. 2017 Aug;58(8):1872-1879. doi: 10.1080/10428194.2016.1263842. Epub 2017 Jan 31.

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

Author information

1
a Abramson Cancer Center , University of Pennsylvania, Perelman School of Medicine , Philadelphia , PA , USA.
2
b Adult Leukemia and Bone Marrow Transplantation Program , University of California San Francisco , San Francisco , CA , USA.
3
c Bone Marrow Transplantation and Leukemia Section, Department of Medicine , Washington University School of Medicine , St. Louis , MO , USA.
4
d Adult Blood and Marrow Transplant Program , Medical College of Wisconsin , Milwaukee , WI , USA.
5
e Division of Hematology and Medical Oncology , Mayo Clinic , Scottsdale , AZ , USA.
6
f John Theurer Cancer Center , Hackensack University Medical Center , Hackensack , NJ , USA.
7
g Department of Hematology , ZNA Stuivenberg , Antwerp , Belgium.
8
h Department of Hematology , University Hospital Leuven , Leuven , Belgium.
9
i Division of Medicine-Cell Therapy and Hematologica , Duke University Medical Center , Durham , NC , USA.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01023880.

KEYWORDS:

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

PMID:
28140719
DOI:
10.1080/10428194.2016.1263842
[Indexed for MEDLINE]

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