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An open-label, multicenter study of oral nilotinib in adult patients with imatinib-resistant or imatinib-intolerant philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase
Article first published online: 5 JUL 2011
Copyright © 2011 American Cancer Society
Volume 118, Issue 1, pages 118–126, 1 January 2012
How to Cite
Nicolini, F. E., Turkina, A., Shen, Z.-X., Gallagher, N., Jootar, S., Powell, B. L., De Souza, C., Zheng, M., Szczudlo, T. and le Coutre, P. (2012), Expanding Nilotinib Access in Clinical Trials (ENACT). Cancer, 118: 118–126. doi: 10.1002/cncr.26249
Presented in part at the 2009 European Hematology Association Annual Congress, Berlin, Germany, June 4–7, 2009, and at the 2009 American Society of Hematology Annual Meeting, New Orleans, LA, USA, December 5–8, 2009.
This trial is registered at www.clinicaltrials.gov as NCT0030216.
We thank Analysis Group, Inc., Boston, Massachusetts for conducting and assisting with statistical analyses; Dr. Coralie Belanger, Novartis Pharma France for her assistance in retrospectively collecting the molecular data from the French dataset; the French molecular biologists of the Groupe des Biologistes Moleculaires des Hémopathies Malignes (Hematopoietic Malignancies Molecular Biologists Group) for their kind help; and Michelle Boehm, PhD, Erinn Goldman, PhD, and Michael Mandola, PhD for medical editorial assistance with the manuscript.
See related articles:
- Issue published online: 16 DEC 2011
- Article first published online: 5 JUL 2011
- Manuscript Accepted: 13 APR 2011
- Manuscript Revised: 31 MAR 2011
- Manuscript Received: 7 JAN 2011
- chronic myeloid leukemia;
- chronic phase;
Nilotinib is a selective, potent BCR-ABL inhibitor. Previous studies demonstrated the efficacy and safety of nilotinib in Philadelphia chromosome-positive chronic myeloid leukemia patients in chronic phase (CML-CP) or accelerated phase who failed prior imatinib.
This expanded access trial further characterized the safety of nilotinib 400 mg twice daily in patients with CML-CP (N = 1422).
In this large, heavily pretreated population, nilotinib demonstrated significant efficacy, with complete hematologic response and complete cytogenetic response achieved in 43% and 34% of patients, respectively. Responses were rapid, mostly occurring within 6 months, and were higher in patients with suboptimal response to imatinib, with 75% and 50% achieving major cytogenetic response and complete cytogenetic response, respectively. At 18 months, the progression-free survival rate was 80%. Most patients achieved planned dosing of 400 mg twice daily and maintained the dose >12 months. Nonhematologic adverse events (AEs) were mostly mild to moderate and included rash (28%), headache (25%), and nausea (17%). Grade 3 or 4 thrombocytopenia (22%), neutropenia (14%), and anemia (3%) were low and managed by dose reduction or brief interruption. Grade 3 or 4 elevations in serum bilirubin and lipase occurred in 4% and 7% of patients, respectively. The incidence of newly occurring AEs decreased over time. Of patients who experienced a dose reduction because of AEs and attempted a re-escalation, 87% successfully achieved re-escalation to the full dose.
This large study confirms that nilotinib was well tolerated and that grade 3 or 4 AEs occurred infrequently and were manageable through transient dose interruptions. Cancer 2012;. © 2011 American Cancer Society.