General AML

A phase I/II study of clofarabine or fludarabine add-on therapy for adults with R/R AML

On 20th July 2017, in a study published in Leukemia and Lymphoma, Nicholas Short and colleagues from The University of Texas MD Anderson Cancer Center, Houston, Texas, reported findings from their phase I/II randomized study (NCT01289457), which evaluated the safety and efficacy of idarubicin and cytarabine with nucleoside analogues clofarabine (CIA) or fludarabine (FIA) therapy for adults with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML).

Initially, the optimal dose of clofarabine for the CIA regimen was investigated in the phase I portion of this trial and the recommended phase II dose for clofarabine was established as 15mg/m2 IV daily on days 1–3. In the phase II portion of the study, a total of 81 R/R AML patients were enrolled between August 2011 and April 2014. Patients were randomly assigned to receive either CIA (median age = 54 years [n =48]) and FIA (median age = 57 years [n = 33]).  

The key results of the phase II study were:
  • Complete Remission (CR)/CR without platelet recovery (CRp) rate in patients in the CIA and FIA arms; 38% vs 30%, P = 0.50
  • Median Event Free Survival (EFS) in patients in the CIA and FIA arms; 2.0 months vs 1.0 months, P = 0.48
  • Median Overall Survival (OS) in CIA and FIA arms; 6.3 vs 4.7 months, P = 0.28
  • Most common grade 3 or 4 Adverse Events (AEs) were infection (CIA 71% vs FIA 63%) and febrile neutropenia (CIA 44% vs FIA 27%)
  • 60-day mortality rate in patients in the CIA and FIA arm; 17% vs 15%, P = 0.86

There were no major differences between the CIA and FIA treatment regimens in terms of AEs and early mortality rates, thus resulting in similar responses and survival rates.

The authors concluded by highlighting that the results of their study suggests that “CIA and FIA are safe and effective salvage treatments” for patients with R/R AML.


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.

  1. Short N.J. et al. 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. 2017 Jul 18: 1–8. DOI: 10.1080/10428194.2017.1349907. [Epub ahead of print].
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