Phase II study of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia.
OBJECTIVE
To evaluate the efficacy and safety of clofarabine, a novel deoxyadenosine analog, in pediatric patients with refractory or relapsed acute lymphoblastic leukemia (ALL).


METHODS
In a phase II, open-label, multicenter study, 61 pediatric patients with refractory or relapsed ALL received clofarabine 52 mg/m2 intravenously over 2 hours daily for 5 days, every 2 to 6 weeks. The median age was 12 years (range, 1 to 20 years), and the median number of prior regimens was three (range, two to six regimens).


RESULTS
The response rate was 30%, consisting of seven complete remissions (CR), five CRs without platelet recovery (CRp), and six partial remissions. Remissions were durable enough to allow patients to proceed to hematopoietic stem-cell transplantation (HSCT) after clofarabine. Median CR duration in patients who did not receive HSCT was 6 weeks, with four patients maintaining CR or CRp for 8 weeks or more (8+, 12, 37+, and 48 weeks) on clofarabine therapy alone. The most common adverse events of grade > or = 3 were febrile neutropenia, anorexia, hypotension, and nausea.


CONCLUSIONS
Clofarabine is active as a single agent in pediatric patients with multiple relapsed or refractory ALL. The toxicity profile is as expected in this heavily pretreated patient population. Studies exploring rational combinations of clofarabine with other agents are ongoing in an effort to maximize clinical benefit.
Jeha
Sima
S
Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA. sima.jeha@stjude.org
Gaynon
Paul S
PS
Razzouk
Bassem I
BI
Franklin
Janet
J
Kadota
Richard
R
Shen
Violet
V
Luchtman-Jones
Lori
L
Rytting
Michael
M
Bomgaars
Lisa R
LR
Rheingold
Susan
S
Ritchey
Kim
K
Albano
Edythe
E
Arceci
Robert J
RJ
Goldman
Stewart
S
Griffin
Timothy
T
Altman
Arnold
A
Gordon
Bruce
B
Steinherz
Laurel
L
Weitman
Steven
S
Steinherz
Peter
P
D000227:Adenine Nucleotides; D000293:Adolescent; D000328:Adult; D001087:Arabinonucleosides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D000077866:Clofarabine; D005260:Female; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D012008:Recurrence; D016896:Treatment Outcome
D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D000077866:Clofarabine