A phase I/II randomized trial of clofarabine or fludarabine added to idarubicin and cytarabine for adults with relapsed or refractory acute myeloid leukemia

Leuk Lymphoma. 2018 Apr;59(4):813-820. doi: 10.1080/10428194.2017.1349907. Epub 2017 Jul 18.

Abstract

The purine nucleoside analogues clofarabine and fludarabine are active in acute myeloid leukemia (AML). We conducted a phase I/II randomized study of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) for relapsed or refractory AML. Clofarabine 15 mg/m2 was identified as the recommended phase II dose. Eighty-one patients were assigned using adaptive randomization to CIA (n = 48) or FIA (n = 33). The complete response (CR)/CR without platelet recovery rate did not differ between CIA and FIA (38% versus 30%, respectively; p = .50). In both arms, more than half of patients who had received only one prior line of therapy achieved remission. The median event-free survival for CIA and FIA was 2.0 and 1.9 months (p = .48), and the median overall survival was 6.3 and 4.7 months, respectively (p = .28). No significant differences in adverse events or early mortality rates were observed. Overall, CIA and FIA resulted in similar response rates and survival in patients with relapsed/refractory AML.

Keywords: Acute myeloid leukemia; clofarabine; fludarabine; purine nucleoside analogues; refractory; relapsed.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Marrow / pathology
  • Clofarabine / pharmacology
  • Clofarabine / therapeutic use*
  • Cytarabine / pharmacology
  • Cytarabine / therapeutic use*
  • Drug Resistance, Neoplasm
  • Humans
  • Idarubicin / pharmacology
  • Idarubicin / therapeutic use*
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / pathology
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Progression-Free Survival
  • Remission Induction / methods
  • Survival Rate
  • Treatment Outcome
  • Vidarabine / analogs & derivatives*
  • Vidarabine / pharmacology
  • Vidarabine / therapeutic use
  • Young Adult

Substances

  • Cytarabine
  • Clofarabine
  • Vidarabine
  • fludarabine
  • Idarubicin