Phase II study of clofarabine in pediatric patients with refractory or relapsed acute myeloid leukemia.
OBJECTIVE
To determine the efficacy and safety of clofarabine in pediatric patients with refractory or relapsed acute myeloid leukemia (AML).


METHODS
A phase II, open-label, multicenter study was conducted with single-agent clofarabine in pediatric patients with refractory or relapsed AML. Clofarabine was administered intravenously over 2 hours at the pediatric maximum-tolerated dose (MTD) of 52 mg/m(2) daily for 5 consecutive days. Cycles were repeated every 2 to 6 weeks. Responses determined by an independent response review panel.


RESULTS
The 42 patients treated on the study had a median age of 13 years (range, 2 to 22 years) and had received a median number of two (range, one to five) prior regimens. The response rate was 26% and included one complete response without platelet recovery and 10 partial responses. The median duration of response was 20 weeks (range, 2 to >or= 156 weeks). Six of 28 patients who were refractory to the immediately preceding therapy achieved response. Thirteen patients (31%), including seven responders, proceeded to hematopoietic stem-cell transplantation (HSCT) after treatment with clofarabine and survived between 24 to >or= 160 weeks. Five patients (12%) remain alive post-transplantation at >or= 63, >or= 71, >or= 86, >or= 114, and >or= 130 weeks. The most common grade 3 or greater adverse events without regard to causality were febrile neutropenia, catheter-related infection, epistaxis, hypotension, nausea, and fever. Transient elevation of liver enzymes and hypokalemia occurred frequently. Five patients died within 30 days of clofarabine administration secondary to progressive disease, and another five died as a result of an adverse event.


CONCLUSIONS
Clofarabine is active in pediatric patients with multiply relapsed or refractory AML. Responses allowed several refractory patients to proceed to HSCT. The toxicity profile was expected in this patient population.
Jeha
Sima
S
Department of Oncology, St Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105, USA. sima.jeha@stjude.org
Razzouk
Bassem
B
Rytting
Michael
M
Rheingold
Susan
S
Albano
Edythe
E
Kadota
Richard
R
Luchtman-Jones
Lori
L
Bomgaars
Lisa
L
Gaynon
Paul
P
Goldman
Stewart
S
Ritchey
Kim
K
Arceci
Robert
R
Altman
Arnold
A
Stine
Kimo
K
Steinherz
Laurel
L
Steinherz
Peter
P
D000208:Acute Disease; D000227:Adenine Nucleotides / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001087:Arabinonucleosides / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D000077866:Clofarabine; D019008:Drug Resistance, Neoplasm; D005260:Female; D005334:Fever / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D009325:Nausea / Q000209:etiology; D009503:Neutropenia / Q000209:etiology; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome; D055815:Young Adult
D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D000077866:Clofarabine