Annals of Hematology

, Volume 92, Issue 8, pp 1049–1056

High-dose imatinib versus high-dose imatinib in combination with intermediate-dose cytarabine in patients with first chronic phase myeloid leukemia: a randomized phase III trial of the Dutch-Belgian HOVON study group

  • Noortje Thielen
  • Bronno van der Holt
  • Gregor E. G. Verhoef
  • Rianne A. H. M. Ammerlaan
  • Pieter Sonneveld
  • Jeroen J. W. M. Janssen
  • Wendy Deenik
  • J. H. Frederik Falkenburg
  • Marie José Kersten
  • Harm A. M. Sinnige
  • Martin Schipperus
  • Anton Schattenberg
  • Rien van Marwijk Kooy
  • Willem M. Smit
  • Isabel W. T. Chu
  • Peter J. M. Valk
  • Gert J. Ossenkoppele
  • Jan J. Cornelissen
Original Article

DOI: 10.1007/s00277-013-1730-4

Cite this article as:
Thielen, N., van der Holt, B., Verhoef, G.E.G. et al. Ann Hematol (2013) 92: 1049. doi:10.1007/s00277-013-1730-4

Abstract

Despite the revolutionary change in the prognosis of chronic myeloid leukemia (CML) patients with the introduction of imatinib, patients with resistant disease still pose a considerable problem. In this multicenter, randomized phase III trial, we investigate whether the combination of high-dose imatinib and intermediate-dose cytarabine compared to high-dose imatinib alone, improves the rate of major molecular response (MMR) in newly diagnosed CML patients. This study was closed prematurely because of declining inclusion due to the introduction of second generation tyrosine kinase inhibitors and only one third of the initially required patients were accrued. One hundred nine patients aged 18–65 years were randomly assigned to either imatinib 800 mg (n = 55) or to imatinib 800 mg in combination with two successive cycles of cytarabine 200 mg/m2 for 7 days (n = 54). After a median follow-up of 41 months, 67 % of patients were still on protocol treatment. The MMR rate at 12 months was 56 % in the imatinib arm and 48 % in the combination arm (p = 0.39). Progression-free survival was 96 % after 1 year and 89 % after 4 years. Four-year overall survival was 97 %. Adverse events grades 3 and 4 were more common in the combination arm. The addition of intermediate-dose of cytarabine to imatinib did not improve the MMR rate at 12 months. However, the underpowering of the study precludes any definitive conclusions. This trial is registered at www.trialregister.nl (NTR674).

Keywords

Chronic myeloid leukemiaImatinibCytarabineMajor molecular response

Supplementary material

277_2013_1730_MOESM1_ESM.doc (618 kb)
ESM 1(DOC 617 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Noortje Thielen
    • 1
  • Bronno van der Holt
    • 2
  • Gregor E. G. Verhoef
    • 3
  • Rianne A. H. M. Ammerlaan
    • 2
  • Pieter Sonneveld
    • 4
  • Jeroen J. W. M. Janssen
    • 1
  • Wendy Deenik
    • 5
  • J. H. Frederik Falkenburg
    • 6
  • Marie José Kersten
    • 7
  • Harm A. M. Sinnige
    • 8
  • Martin Schipperus
    • 9
  • Anton Schattenberg
    • 10
  • Rien van Marwijk Kooy
    • 11
  • Willem M. Smit
    • 12
  • Isabel W. T. Chu
    • 4
  • Peter J. M. Valk
    • 4
  • Gert J. Ossenkoppele
    • 1
  • Jan J. Cornelissen
    • 4
  1. 1.Department of HematologyVU University Medical CenterAmsterdamthe Netherlands
  2. 2.HOVON Data CenterErasmus University Medical Center-Daniel den HoedRotterdamthe Netherlands
  3. 3.Department of HematologyUniversity Hospital GasthuisbergLeuvenBelgium
  4. 4.Department of HematologyErasmus University Medical CenterRotterdamthe Netherlands
  5. 5.Department of Internal MedicineTergooiziekenhuizenHilversumthe Netherlands
  6. 6.Department of HematologyLeiden University Medical CenterLeidenthe Netherlands
  7. 7.Department of HematologyAcademic Medical CenterAmsterdamthe Netherlands
  8. 8.Department of HematologyJeroen Bosch Hospital‘s-Hertogenboschthe Netherlands
  9. 9.Department of HematologyHaga Hospitalthe Haguethe Netherlands
  10. 10.Department of HematologyRadboud University Nijmegen Medical CenterNijmegenthe Netherlands
  11. 11.Department of Internal MedicineIsala KliniekenZwollethe Netherlands
  12. 12.Department of Internal MedicineMedisch Spectrum TwenteEnschedethe Netherlands