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Leukemia & Lymphoma Volume 58, 2017 - Issue 6
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Original Articles: Clinical

The CDK inhibitor AT7519M in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and mantle cell lymphoma. A Phase II study of the Canadian Cancer Trials Group

Matthew D. SeftelDepartment of Medical Oncology and Hematology, CancerCare Manitoba and University of Manitoba, Winnipeg, MB, Canada; Correspondence[email protected]
,
John KuruvillaDepartment of Medical Oncology and Hematology, Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada;
,
Tom KouroukisDepartment of Oncology, Juravinski Cancer Centre and McMaster University, Hamilton, ON, Canada;
,
Versha BanerjiDepartment of Medical Oncology and Hematology, CancerCare Manitoba and University of Manitoba, Winnipeg, MB, Canada;
,
Graeme FraserDepartment of Oncology, Juravinski Cancer Centre and McMaster University, Hamilton, ON, Canada;
,
Michael CrumpDepartment of Medical Oncology and Hematology, Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada;
,
Rajat KumarDepartment of Medical Oncology and Hematology, CancerCare Manitoba and University of Manitoba, Winnipeg, MB, Canada;
,
Haji I. ChalchalDepartment of Hematology, Allan Blair Cancer Centre, Regina, SK, Canada; ;University of Saskatchewan, Saskatchewan, SK, Canada;
,
Muhammad SalimDepartment of Hematology, Allan Blair Cancer Centre, Regina, SK, Canada; ;University of Saskatchewan, Saskatchewan, SK, Canada;
,
Rob C. LaisterDepartment of Medical Oncology and Hematology, Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada;
,
Susan CrockerDepartment of Pathology and Molecular Medicine, Queen’s University, Kingston, ON, Canada;
,
Spencer B. GibsonResearch Institute of Oncology and Hematology, CancerCare Manitoba and Department of Biochemistry, University of Manitoba, Winnipeg, MB, Canada;
,
Marcia ToguchiAstex Pharmaceuticals, Cambridge, UK;
,
John F. LyonsAstex Pharmaceuticals, Cambridge, UK;
,
Hao XuCanadian Cancer Trials Group, Queen’s University, Kingston, ON, Canada;
,
Jean PowersCanadian Cancer Trials Group, Queen’s University, Kingston, ON, Canada;
,
Joana SederiasCanadian Cancer Trials Group, Queen’s University, Kingston, ON, Canada;
,
Lesley SeymourCanadian Cancer Trials Group, Queen’s University, Kingston, ON, Canada;
&
Annette E. HayCanadian Cancer Trials Group, Queen’s University, Kingston, ON, Canada; ;Department of Medicine, Queen’s University, Kingston, ON, Canada
 show all
Pages 1358-1365 | Received 04 May 2016, Accepted 11 Sep 2016, Published online: 17 Oct 2016
 
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Abstract

AT7519M is a small molecule inhibitor of cyclin-dependent kinases 1, 2, 4, 5, and 9 with in vitro activity against lymphoid malignancies. In two concurrent Phase II trials, we evaluated AT7519M in relapsed or refractory chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) using the recommended Phase II dosing of 27 mg/m2 twice weekly for 2 of every 3 weeks. Primary objective was objective response rate (ORR). Nineteen patients were accrued (7 CLL, 12 MCL). Four CLL patients achieved stable disease (SD). Two MCL patients achieved partial response (PR), and 6 had SD. One additional MCL patient with SD subsequently achieved PR 9 months after completion of AT7519M. Tumor lysis syndrome was not reported. In conclusion, AT7519M was safely administered to patients with relapsed/refractory CLL and MCL. In CLL, some patients had tumor reductions, but the ORR was low. In MCL, activity was noted with ORR of 27%.

Acknowledgements

The authors would like to thank the patients and clinical trials support staff at all participating sites. The Canadian Cancer Trials Group (CCTG) is supported by a grant from the Canadian Cancer Society. Astex Pharmaceuticals provided funding to support this trial.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2016.1239259.

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