Phase i dose escalation trial of the novel proteasome inhibitor carfilzomib in patients with relapsed chronic lymphocytic leukemia and small lymphocytic lymphoma

Farrukh T. Awan, Joseph M. Flynn, Jeffrey A. Jones, Leslie A. Andritsos, Kami J. Maddocks, Ellen J. Sass, Margaret S. Lucas, Weihong Chase, Sharon Waymer, Yonghua Ling, Yao Jiang, Mitch A. Phelps, John C. Byrd, David M. Lucas, Jennifer A. Woyach

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The proteasome complex degrades proteins involved in a variety of cellular processes and is a powerful therapeutic target in several malignancies. Carfilzomib is a potent proteasome inhibitor which induces rapid chronic lymphocytic leukemia (CLL) cell apoptosis in vitro. We conducted a phase I dose-escalation trial to determine the safety and tolerability of carfilzomib in relapsed/refractory CLL or small lymphocytic lymphoma (SLL). Nineteen patients were treated with carfilzomib initially at 20 mg/m 2 , then escalated in four cohorts (27, 36, 45 and 56 mg/m 2 ) on days 1, 2, 8, 9, 15 and 16 of 28-day cycles. Therapy was generally well tolerated, and no dose limiting toxicities were observed. The most common hematologic toxicities were thrombocytopenia and neutropenia. All patients evaluable for response had stable disease, including patients with del17p13 and fludarabine-resistant disease. This trial shows acceptable tolerability and limited preliminary efficacy of carfilzomib in CLL and SLL.

Original languageEnglish (US)
Pages (from-to)2834-2840
Number of pages7
JournalLeukemia and Lymphoma
Volume56
Issue number10
DOIs
StatePublished - Oct 3 2015
Externally publishedYes

Fingerprint

Proteasome Inhibitors
B-Cell Chronic Lymphocytic Leukemia
Proteasome Endopeptidase Complex
Neutropenia
Thrombocytopenia
carfilzomib
Apoptosis
Safety
Therapeutics
Neoplasms
Proteins

Keywords

  • carfilzomib
  • chronic lymphocytic leukemia
  • Proteasome inhibitor

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Phase i dose escalation trial of the novel proteasome inhibitor carfilzomib in patients with relapsed chronic lymphocytic leukemia and small lymphocytic lymphoma. / Awan, Farrukh T.; Flynn, Joseph M.; Jones, Jeffrey A.; Andritsos, Leslie A.; Maddocks, Kami J.; Sass, Ellen J.; Lucas, Margaret S.; Chase, Weihong; Waymer, Sharon; Ling, Yonghua; Jiang, Yao; Phelps, Mitch A.; Byrd, John C.; Lucas, David M.; Woyach, Jennifer A.

In: Leukemia and Lymphoma, Vol. 56, No. 10, 03.10.2015, p. 2834-2840.

Research output: Contribution to journalArticle

Awan, FT, Flynn, JM, Jones, JA, Andritsos, LA, Maddocks, KJ, Sass, EJ, Lucas, MS, Chase, W, Waymer, S, Ling, Y, Jiang, Y, Phelps, MA, Byrd, JC, Lucas, DM & Woyach, JA 2015, 'Phase i dose escalation trial of the novel proteasome inhibitor carfilzomib in patients with relapsed chronic lymphocytic leukemia and small lymphocytic lymphoma', Leukemia and Lymphoma, vol. 56, no. 10, pp. 2834-2840. https://doi.org/10.3109/10428194.2015.1014368
Awan, Farrukh T. ; Flynn, Joseph M. ; Jones, Jeffrey A. ; Andritsos, Leslie A. ; Maddocks, Kami J. ; Sass, Ellen J. ; Lucas, Margaret S. ; Chase, Weihong ; Waymer, Sharon ; Ling, Yonghua ; Jiang, Yao ; Phelps, Mitch A. ; Byrd, John C. ; Lucas, David M. ; Woyach, Jennifer A. / Phase i dose escalation trial of the novel proteasome inhibitor carfilzomib in patients with relapsed chronic lymphocytic leukemia and small lymphocytic lymphoma. In: Leukemia and Lymphoma. 2015 ; Vol. 56, No. 10. pp. 2834-2840.
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