AAML0523: a report from the Children's Oncology Group on the efficacy of clofarabine in combination with cytarabine in pediatric patients with recurrent acute myeloid leukemia

Cancer. 2014 Aug 15;120(16):2482-9. doi: 10.1002/cncr.28674. Epub 2014 Apr 25.


Background: The discovery of new, effective non-anthracycline-based reinduction regimens for children with recurrent acute myeloid leukemia (AML) is critical. In this phase 1/2 study, the tolerability and overall response rate of clofarabine in combination with cytarabine was investigated in children with recurrent/refractory AML.

Methods: AAML0523 enrolled 49 children with AML in first recurrence or who were refractory to induction therapy. The study consisted of a dose-finding phase (9 patients) and an efficacy phase (40 patients). Two children received clofarabine at a dose of 40 mg/m(2)/day and 47 children at a dose of 52 mg/m(2)/day.

Results: Toxicities typical for intensive chemotherapy regimens were observed at all doses of clofarabine. The recommended pediatric phase 2 dose of clofarabine in combination with cytarabine was 52 mg/m(2)/day for 5 days. Of 48 evaluable patients, the overall response rate (complete remission plus complete remission with partial platelet recovery) was 48%. Four patients met conventional criteria for complete remission with incomplete count recovery. Twenty-one of 23 responders subsequently underwent hematopoietic stem cell transplantation. The overall survival rate at 3 years was 46% for responders compared with 16% for nonresponders (P < .001). Patients found to have no minimal residual disease at the end of the first cycle by flow cytometric analysis had superior overall survival after 1 year (100% vs 38%; P = .01).

Conclusions: The combination of clofarabine and cytarabine yielded an acceptable response rate without excess toxicity in children with recurrent AML. The nearly 50% survival rate reported in responders is highly encouraging in these high-risk patients and suggests that this combination is an effective bridge to hematopoietic stem cell transplantation.

Keywords: acute myeloid leukemia; clofarabine; cytarabine; pediatric.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenine Nucleotides / administration & dosage
  • Adenine Nucleotides / adverse effects
  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Arabinonucleosides / administration & dosage
  • Arabinonucleosides / adverse effects
  • Child
  • Child, Preschool
  • Clofarabine
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Male
  • Young Adult


  • Adenine Nucleotides
  • Arabinonucleosides
  • Cytarabine
  • Clofarabine