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. Issue 16 (25th April 2014)

• Record Type: Journal Article
• Authors: Cooper, Todd M.; Alonzo, Todd A.; Gerbing, Robert B.; Perentesis, John P.; Whitlock, James A.; Taub, Jeffrey W.; Horton, Terzah M.; Gamis, Alan S.; Meshinchi, Soheil; Loken, Michael R.; Razzouk, Bassem I.
• Is Part Of: Cancer. Volume 120:Issue 16(2014)
• Page Start: 2482
• Page End: 2489
• Publication Date: 2014-04-25
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.28674
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cncr28674-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>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.</p> </sec> <sec id="cncr28674-sec-0002" sec-type="section"> <title>METHODS</title> <p>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<sup>2</sup>/day and 47 children at a dose of 52 mg/m<sup>2</sup>/day.</p> </sec> <sec id="cncr28674-sec-0003" sec-type="section"> <title>RESULTS</title> <p>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<sup>2</sup>/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 (<italic>P</italic> < .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%; <italic>P</italic> = .01).</p> </sec> <sec id="cncr28674-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>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. <bold><italic>Cancer</italic> 2014;120:2482–2489.</bold> © <italic>2014 American Cancer Society</italic>.</p> </sec> </abstract>