title: Phase I/II trial of clofarabine and cytarabine in children with relapsed/refractory acute lymphoblastic leukemia (AAML0523): a report from the Children's Oncology Group.
abstract: BACKGROUND
  The discovery of effective re-induction regimens for children with more than one relapse of acute lymphoblastic leukemia (ALL) remains elusive. The novel nucleoside analog clofarabine exhibits modest single agent efficacy in relapsed ALL, though optimal combinations of this agent with other active chemotherapy drugs have not yet been defined. Herein we report the response rates of relapsed ALL patients treated on Children's Oncology Group study AAML0523, a Phase I/II study of the combination of clofarabine and cytarabine.
  
  
  METHODS
  AAML0523 enrolled 21 children with ALL in second or third relapse, or those refractory to re-induction therapy. The study consisted of two phases: a dose finding phase and an efficacy phase. The dose finding portion consisted of a single dose escalation/de-escalation of clofarabine for 5 days in combination with a fixed dose of cytarabine (1 g/m(2)/day for 5 days). Eight patients received clofarabine at 40 mg/m(2)/day and 13 patients at 52 mg/m(2)/day.
  
  
  RESULTS
  Toxicities observed at all doses of clofarabine were typical of intensive chemotherapy regimens for leukemia, with infection being the most common. We did not observe significant hepatotoxicity as reported in other clofarabine combination regimens. The recommended pediatric Phase II dose of clofarabine in combination with cytarabine for the efficacy portion of AAML0523 was 52 mg/m(2). Of 21 patients with ALL, 3 (14%) achieved a complete response (CR). Based on the two-stage design definition of first-stage inactivity, the therapy was deemed ineffective.
  
  
  CONCLUSIONS
  The combination of clofarabine and cytarabine in relapsed/refractory childhood ALL does not warrant further clinical investigation.
authors: Aflac Cancer and Blood Disorders Center/Children's Healthcare of Atlanta/Emory University, Atlanta, Georgia 30322, USA. todd.cooper@choa.org
authors: Todd M
authors: TM
authors: Cooper
authors: Bassem I
authors: BI
authors: Razzouk
authors: Robert
authors: R
authors: Gerbing
authors: Todd A
authors: TA
authors: Alonzo
authors: Kathleen
authors: K
authors: Adlard
authors: Elizabeth
authors: E
authors: Raetz
authors: Alan S
authors: AS
authors: Gamis
authors: John
authors: J
authors: Perentesis
authors: James A
authors: JA
authors: Whitlock
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001087:Arabinonucleosides / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D000077866:Clofarabine; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality; D055815:Young Adult
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D003561:Cytarabine; D000077866:Clofarabine