title: 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.
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/m2twice 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%.
authors.affiliation: a Department of Medical Oncology and Hematology , CancerCare Manitoba and University of Manitoba , Winnipeg , MB , Canada.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Seftel
authors.affiliation: b Department of Medical Oncology and Hematology , Princess Margaret Cancer Centre and University of Toronto , Toronto , ON , Canada.
authors.forename: John
authors.initials: J
authors.lastname: Kuruvilla
authors.affiliation: c Department of Oncology , Juravinski Cancer Centre and McMaster University , Hamilton , ON , Canada.
authors.forename: Tom
authors.initials: T
authors.lastname: Kouroukis
authors.affiliation: a Department of Medical Oncology and Hematology , CancerCare Manitoba and University of Manitoba , Winnipeg , MB , Canada.
authors.forename: Versha
authors.initials: V
authors.lastname: Banerji
authors.affiliation: c Department of Oncology , Juravinski Cancer Centre and McMaster University , Hamilton , ON , Canada.
authors.forename: Graeme
authors.initials: G
authors.lastname: Fraser
authors.affiliation: b Department of Medical Oncology and Hematology , Princess Margaret Cancer Centre and University of Toronto , Toronto , ON , Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Crump
authors.affiliation: a Department of Medical Oncology and Hematology , CancerCare Manitoba and University of Manitoba , Winnipeg , MB , Canada.
authors.forename: Rajat
authors.initials: R
authors.lastname: Kumar
authors.affiliation: d Department of Hematology , Allan Blair Cancer Centre , Regina , SK , Canada.|e University of Saskatchewan , Saskatchewan , SK , Canada.
authors.forename: Haji I
authors.initials: HI
authors.lastname: Chalchal
authors.affiliation: d Department of Hematology , Allan Blair Cancer Centre , Regina , SK , Canada.|e University of Saskatchewan , Saskatchewan , SK , Canada.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Salim
authors.affiliation: b Department of Medical Oncology and Hematology , Princess Margaret Cancer Centre and University of Toronto , Toronto , ON , Canada.
authors.forename: Rob C
authors.initials: RC
authors.lastname: Laister
authors.affiliation: f Department of Pathology and Molecular Medicine , Queen's University , Kingston , ON , Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Crocker
authors.affiliation: g Research Institute of Oncology and Hematology, CancerCare Manitoba and Department of Biochemistry , University of Manitoba , Winnipeg , MB , Canada.
authors.forename: Spencer B
authors.initials: SB
authors.lastname: Gibson
authors.affiliation: h Astex Pharmaceuticals , Cambridge , UK.
authors.forename: Marcia
authors.initials: M
authors.lastname: Toguchi
authors.affiliation: h Astex Pharmaceuticals , Cambridge , UK.
authors.forename: John F
authors.initials: JF
authors.lastname: Lyons
authors.affiliation: i Canadian Cancer Trials Group , Queen's University , Kingston , ON , Canada.
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.affiliation: i Canadian Cancer Trials Group , Queen's University , Kingston , ON , Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Powers
authors.affiliation: i Canadian Cancer Trials Group , Queen's University , Kingston , ON , Canada.
authors.forename: Joana
authors.initials: J
authors.lastname: Sederias
authors.affiliation: i Canadian Cancer Trials Group , Queen's University , Kingston , ON , Canada.
authors.forename: Lesley
authors.initials: L
authors.lastname: Seymour
authors.affiliation: i Canadian Cancer Trials Group , Queen's University , Kingston , ON , Canada.|j Department of Medicine , Queen's University , Kingston , ON , Canada.
authors.forename: Annette E
authors.initials: AE
authors.lastname: Hay
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers; D002170:Canada; D002869:Chromosome Aberrations; D003131:Combined Modality Therapy; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012008:Recurrence; D019233:Retreatment
chemical_list: D015415:Biomarkers; D047428:Protein Kinase Inhibitors; D018844:Cyclin-Dependent Kinases
keywords: Chronic lymphocytic leukemia; cyclin-dependent kinase inhibitors; mantle cell lymphoma