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

• Type of Material: Article
• Authors: Todd Cooper, Emory University; TA Alonzo, University of Southern California; RB Gerbing, Children's Oncology Group; J Perentesis, Cincinnati Children's Hospital Medical Center; J Whitlock, University of Toronto; JW Taub, Children's Hospital Michigan; TM Horton, Baylor College of Medicine; A Gamis, Children's Mercy Hospitals and Clinics; S Meshinchi, Fred Hutchinson Cancer Research Center; MR Loken, HematoLogics Inc.; B I. Razzouk, Peyton Manning Children’s Hospital at St. Vincent
• Language: English
• Date: 2014-08-15
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 American Cancer Society.
• Final Published Version (URL): http://dx.doi.org/10.1002/cncr.28674
• Title of Journal or Parent Work: Cancer
• ISSN: 0008-543X
• Volume: 120
• Issue: 16
• Start Page: 2482
• End Page: 2489
• Grant/Funding Information: The work was supported by National Institute of Health Grants: Children's Oncology Group Chair's grant NIH U10 CA98543 and SDC U10 CA98413.
• Keywords: ETOPOSIDE; Science & Technology; ACUTE LYMPHOBLASTIC-LEUKEMIA; CANCER; Oncology; Life Sciences & Biomedicine; THERAPY; clofarabine; acute myeloid leukemia; cytarabine; TRIAL; RISK; pediatric
• Research Categories: Health Sciences, Oncology

Abstract

BACKGROUND: 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. METHODS: 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/day and 47 children at a dose of 52 mg/m/day. RESULTS: 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/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 (P<.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%; P=.01). CONCLUSIONS: 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.