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Blood, 1 February 2004, Vol. 103, No. 3, pp. 784-789. Prepublished online as a Blood First Edition Paper on October 9, 2003; DOI 10.1182/blood-2003-06-2122. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-06-2122v1 103/3/784    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jeha, S. Articles by Kantarjian, H. Search for Related Content PubMed PubMed Citation Articles by Jeha, S. Articles by Kantarjian, H. Related Collections Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemia Sima Jeha, Varsha Gandhi, Ka Wah Chan, Lisa McDonald, Irma Ramirez, Renee Madden, Michael Rytting, Mark Brandt, Michael Keating, William Plunkett, and Hagop Kantarjian From the Departments of Pediatrics, Experimental Therapeutics, and Leukemia, University of Texas MD Anderson Cancer Center, Houston. Despite progress in leukemia therapy, most children who experience relapse have a dismal prognosis. New, effective approaches are needed. We conducted a phase 1 study of a novel nucleoside analog, clofarabine, in pediatric patients with refractory and relapsed leukemia. Clofarabine was infused intravenously over 1 hour each day for 5 days. Six dose levels, between 11.25 and 70 mg/m2 per day for 5 days, were studied in 25 patients. A modified 3 + 3 phase 1 design was followed with 30% dose escalation until the dose-limiting toxicity (DLT) was defined. The maximum tolerated dose (MTD) was 52 mg/m2 per day for 5 days. At the end of infusion at MTD, clofarabine triphosphate levels in leukemia blasts varied between 6 µM and 19 µM, which resulted in complete and sustained inhibition of DNA synthesis. The DLT was reversible hepatotoxicity and skin rash at 70 mg/m2 per day for 5 days. Twenty-five patients were treated. Five patients achieved complete remission (CR), and 3 achieved partial remission (PR), for an overall response rate of 32%. Clofarabine is well tolerated and shows significant antileukemic activity in heavily pretreated children. Multicenter phase 2 trials in pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are ongoing. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. E. Karp, R. M. Ricklis, K. Balakrishnan, J. Briel, J. Greer, S. D. Gore, B. D. Smith, M. A. McDevitt, H. Carraway, M. J. Levis, et al. A phase 1 clinical-laboratory study of clofarabine followed by cyclophosphamide for adults with refractory acute leukemias Blood, September 15, 2007; 110(6): 1762 - 1769. [Abstract] [Full Text] [PDF] V. Gandhi, W. Plunkett, P. L. Bonate, M. Du, B. Nowak, S. Lerner, and M. J. Keating Clinical and Pharmacokinetic Study of Clofarabine in Chronic Lymphocytic Leukemia: Strategy for Treatment. Clin. Cancer Res., July 1, 2006; 12(13): 4011 - 4017. [Abstract] [Full Text] [PDF] S. Faderl, S. Verstovsek, J. Cortes, F. Ravandi, M. Beran, G. Garcia-Manero, A. Ferrajoli, Z. Estrov, S. O'Brien, C. Koller, et al. 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Press, and J. Q. Rose THE DISTRIBUTION, METABOLISM, AND ELIMINATION OF CLOFARABINE IN RATS Drug Metab. Dispos., June 1, 2005; 33(6): 739 - 748. [Abstract] [Full Text] [PDF] S. Faderl, V. Gandhi, S. O'Brien, P. Bonate, J. Cortes, E. Estey, M. Beran, W. Wierda, G. Garcia-Manero, A. Ferrajoli, et al. Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias Blood, February 1, 2005; 105(3): 940 - 947. [Abstract] [Full Text] [PDF] P. L. Bonate, A. Craig, P. Gaynon, V. Gandhi, S. Jeha, R. Kadota, G. N. Lam, W. Plunkett, B. Razzouk, M. Rytting, et al. Population Pharmacokinetics of Clofarabine, a Second-Generation Nucleoside Analog, in Pediatric Patients With Acute Leukemia J. Clin. Pharmacol., November 1, 2004; 44(11): 1309 - 1322. [Abstract] [Full Text] [PDF]

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