Originally published as JCO Early Release 10.1200/JCO.2008.18.8706 on August 3 2009

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Phase II Study of Clofarabine in Pediatric Patients With Refractory or Relapsed Acute Myeloid Leukemia

From St Jude Children'ps Research Hospital, Memphis, TN; St Vincent Children'ps Hospital, Indianapolis, IN, The M. D. Anderson Cancer Center; and Texas Children'ps Cancer Center, Houston, TX; Children'ps Hospital of Philadelphia, Philadelphia; and Children'ps Hospital of Pittsburgh, Pittsburgh, PA; Children'ps Hospital at Denver, Denver, CO; Children'ps Hospital of San Diego, San Diego; and Children'ps Hospital of Los Angeles, Los Angeles, CA; Washington University Medical School, St Louis, MO; Children'ps Memorial Hospital, Chicago, IL; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD; Connecticut Children'ps Medical Center, Hartford, CT; Arkansas Children'ps Hospital, Little Rock, AR; and Memorial Sloan-Kettering Cancer Center, New York, NY.

Corresponding author: Sima Jeha, MD, Department of Oncology, St Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105; e-mail: sima.jeha{at}stjude.org.

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

Patients and 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/m² 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 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 160 weeks. Five patients (12%) remain alive post-transplantation at 63, 71, 86, 114, and 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.

Conclusion 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.

Supported in part by a grant from Genzyme Oncology (successor to ILEX Oncology), San Antonio, TX; by Cancer Center Support Grant No. CA21765 from the National Cancer Institute; and by the American Lebanese Syrian Associated Charities.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: NCT00042354 [ClinicalTrials.gov] .

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