Annals of Hematology

, Volume 93, Issue 6, pp 965–975

Clofarabine in combination with a standard remission induction regimen (cytosine arabinoside and idarubicin) in patients with previously untreated intermediate and bad-risk acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS): phase I results of an ongoing phase I/II study of the leukemia groups of EORTC and GIMEMA (EORTC GIMEMA 06061/AML-14A trial)

  • R. Willemze
  • S. Suciu
  • P. Muus
  • C. J. M. Halkes
  • G. Meloni
  • L. Meert
  • M. Karrasch
  • J. Rapion
  • M. Vignetti
  • S. Amadori
  • T. de Witte
  • J. P. Marie
Original Article

DOI: 10.1007/s00277-014-2056-6

Cite this article as:
Willemze, R., Suciu, S., Muus, P. et al. Ann Hematol (2014) 93: 965. doi:10.1007/s00277-014-2056-6
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Abstract

This study aims to determine the maximum tolerated dose (MTD) of clofarabine combined with the EORTC-GIMEMA 3 + 10 induction regimen (idarubicin + cytosine arabinoside) in adults with untreated acute myelogenous leukemia or high-risk myelodysplastic syndrome. In this phase I trial, 25 patients (median age 56 years) received 5 days of clofarabine as 1-h infusion (arm A) or push injection (arm B) at the dose level of 5 × 10 or 5 × 15 mg/m2/day in an algorithmic dose escalation 3 + 3 design. A consolidation course (intermediate dose cytosine arabinoside, idarubicin) was planned for patients in complete remission (CR). Primary endpoint was safety and tolerance as measured by dose limiting toxicity (DLT); secondary endpoints were response rate, other grade III/IV toxicities, and hematological recovery after induction and consolidation. Five DLTs were observed (in arm A: one DLT at 10 mg/m2/day, three at 15 mg/m2/day; in arm B: one DLT at 15 mg/m2/day). Three patients receiving 15 mg/m2/day were withdrawn due to adverse events not classified as DLT. Prolonged hypoplasia was observed in five patients. CR + complete remission with incomplete recovery were achieved in 21 patients (11/12 (92 %) receiving clofarabine 10 mg/m2/day; 10/13 (77 %) receiving clofarabine 15 mg/m2/day). Clofarabine, 5 × 10 mg/m2/day, resulted in one DLT and no early treatment withdrawals. MTD of clofarabine combined with cytosine arabinoside and idarubicin is 5 × 10 mg/m2/day.

Keywords

Acute myeloid leukemiaClofarabinePhase I dose finding study

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • R. Willemze
    • 1
  • S. Suciu
    • 2
  • P. Muus
    • 3
  • C. J. M. Halkes
    • 1
  • G. Meloni
    • 4
  • L. Meert
    • 2
  • M. Karrasch
    • 2
  • J. Rapion
    • 2
  • M. Vignetti
    • 5
  • S. Amadori
    • 6
  • T. de Witte
    • 3
  • J. P. Marie
    • 7
  1. 1.Department of HematologyLeiden University Medical CenterLeidenThe Netherlands
  2. 2.EORTC HeadquartersBrusselsBelgium
  3. 3.Radboud University Medical CenterNijmegenThe Netherlands
  4. 4.University “Sapienza”RomeItaly
  5. 5.GIMEMA Data CenterRomeItaly
  6. 6.Tor Vergata University HospitalRomeItaly
  7. 7.Hopital Saint AntoineParisFrance