The Plk1 inhibitor BI 2536 in patients with refractory or relapsed non-Hodgkin lymphoma: A phase I, open-label, single dose-escalation study

Julie Marie Vose, Jonathan W. Friedberg, Edmund K. Waller, Bruce D. Cheson, Vasthala Juvvigunta, Holger Fritsch, Claude Petit, Gerd Munzert, Anas Younes

Research output: Contribution to journalArticle

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Abstract

Polo-like kinase 1 (Plk1) is expressed during mitosis and overexpressed in multiple cancers, including non-Hodgkin lymphoma (NHL). This phase I study determined the maximum tolerated dose (MTD) of BI 2536, a Plk1 inhibitor, as a 1 h infusion once every 3 weeks in post-transplant relapsed (n = 17) and transplant-naive (n = 24) patients with relapsed/refractory NHL. Median treatment cycles were 2 and 1.5, respectively. MTD was 175 mg for both populations; dose-limiting toxicities were grade 4 thrombocytopenia and neutropenia. Most treatment-related adverse events were grade 1/2; drug-related grade 3/4 events included thrombocytopenia and neutropenia. Four patients achieved responses (three complete and one partial at doses ≥ 150 mg, all post-transplant relapsed patients) for an overall response rate of 9.8%. BI 2536 exhibited multi-compartmental pharmacokinetics with a high volume of distribution. The activity and safety of BI 2536 in this pretreated patient population support Plk inhibitors as a therapeutic strategy in oncology.

Original languageEnglish (US)
Pages (from-to)708-713
Number of pages6
JournalLeukemia and Lymphoma
Volume54
Issue number4
DOIs
StatePublished - Apr 1 2013

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Non-Hodgkin's Lymphoma
Maximum Tolerated Dose
Neutropenia
Transplants
Mitosis
Thrombocytopenia
Population
Therapeutics
Pharmacokinetics
Safety
polo-like kinase 1
BI 2536
Pharmaceutical Preparations
Neoplasms

Keywords

  • BI 2536
  • Non-Hodgkin lymphoma
  • Single dose-escalation study

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

The Plk1 inhibitor BI 2536 in patients with refractory or relapsed non-Hodgkin lymphoma : A phase I, open-label, single dose-escalation study. / Vose, Julie Marie; Friedberg, Jonathan W.; Waller, Edmund K.; Cheson, Bruce D.; Juvvigunta, Vasthala; Fritsch, Holger; Petit, Claude; Munzert, Gerd; Younes, Anas.

In: Leukemia and Lymphoma, Vol. 54, No. 4, 01.04.2013, p. 708-713.

Research output: Contribution to journalArticle

Vose, JM, Friedberg, JW, Waller, EK, Cheson, BD, Juvvigunta, V, Fritsch, H, Petit, C, Munzert, G & Younes, A 2013, 'The Plk1 inhibitor BI 2536 in patients with refractory or relapsed non-Hodgkin lymphoma: A phase I, open-label, single dose-escalation study', Leukemia and Lymphoma, vol. 54, no. 4, pp. 708-713. https://doi.org/10.3109/10428194.2012.729833
Vose, Julie Marie ; Friedberg, Jonathan W. ; Waller, Edmund K. ; Cheson, Bruce D. ; Juvvigunta, Vasthala ; Fritsch, Holger ; Petit, Claude ; Munzert, Gerd ; Younes, Anas. / The Plk1 inhibitor BI 2536 in patients with refractory or relapsed non-Hodgkin lymphoma : A phase I, open-label, single dose-escalation study. In: Leukemia and Lymphoma. 2013 ; Vol. 54, No. 4. pp. 708-713.
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