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01.11.2014 | Original Article

Clinical study of the novel cyclin-dependent kinase inhibitor dinaciclib in combination with rituximab in relapsed/refractory chronic lymphocytic leukemia patients

verfasst von: Claire Fabre, Marco Gobbi, Cyrine Ezzili, Mustapha Zoubir, Marie-Paule Sablin, Karen Small, Ellie Im, Nabeegha Shinwari, Da Zhang, Honghong Zhou, Christophe Le Tourneau

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 5/2014

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Abstract

Purpose

Dinaciclib is a novel selective inhibitor of cyclin-dependent kinase (CDK)1, CDK2, CDK5, and CDK9. We conducted a phase I study to investigate the effects of dinaciclib when administered with rituximab.

Methods

In this phase I nonrandomized dose-escalation 3 + 3 trial, patients with relapsed/refractory chronic lymphocytic leukemia (CLL) were treated with dinaciclib and rituximab. Dinaciclib was administered intravenously (IV) over 2 h on days 1, 8 and 15 in cycles 2–13 (28-day cycles). Rituximab 375 mg/m² was administered IV on days 1, 8, 15 and 22 in cycle 1 (28-day cycle) and on day 1 during cycle 3–13. Rituximab was not administered in cycle 2. Rituximab and dinaciclib were given alone in cycles 1 and 2, respectively, and in combination in cycles 3–13. Primary objectives included determination of the recommended phase II dose of dinaciclib and evaluation of pharmacokinetics (PK) when administered with rituximab.

Results

Five patients completed the study due to early termination. All presented with drug-related adverse events (AEs), but no dose-limiting toxicities were observed. The most commonly observed toxicities included hematological, digestive and metabolic AEs. However, no tumor lysis syndrome has been reported in the study. Four patients achieved stable disease, and one patient achieved complete response according to 2008 iwCLL criteria at cycle 3. PK samples were collected from 5 patients, and no obvious interaction between dinaciclib and rituximab was observed.

Conclusions

Limited data from this study shows dinaciclib in combination with rituximab was well tolerated and revealed encouraging clinical activity in relapsed/refractory CLL patients.

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Titel: Clinical study of the novel cyclin-dependent kinase inhibitor dinaciclib in combination with rituximab in relapsed/refractory chronic lymphocytic leukemia patients
verfasst von: Claire Fabre
Marco Gobbi
Cyrine Ezzili
Mustapha Zoubir
Marie-Paule Sablin
Karen Small
Ellie Im
Nabeegha Shinwari
Da Zhang
Honghong Zhou
Christophe Le Tourneau
Publikationsdatum: 01.11.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 5/2014
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-014-2583-9

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Clinical study of the novel cyclin-dependent kinase inhibitor dinaciclib in combination with rituximab in relapsed/refractory chronic lymphocytic leukemia patients