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

Sima Jeha, Paul S. Gaynon, Bassem I. Razzouk, Janet Franklin, Richard Kadota, Violet Shen, Lori Luchtman-Jones, Michael Rytting, Lisa R. Bomgaars, Susan Rheingold, Kim Ritchey, Edythe Albano, Robert J. Arceci, Stewart Goldman, Timothy Griffin, Arnold Altman, Bruce Gordon, Laurel Steinherz, Steven Weitman, Peter Steinherz

From the St Jude Children's Research Hospital, Memphis, TN; Children's Hospital of Los Angeles, Los Angeles; Children's Hospital of San Diego, San Diego; Children's Hospital of Orange County, Orange, CA; Washington University Medical School, St Louis, MO; M.D. Anderson Cancer Center, Houston; Texas Children's Cancer Center, Houston; Cook's Children's Hospital, Fort Worth; Genzyme Oncology, San Antonio, TX; The Children's Hospital of Philadelphia, Philadelphia; Children's Hospital of Pittsburgh, Pittsburgh, PA; Children's Hospital at Denver, Denver, CO; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD; Children's Memorial Hospital, Chicago, IL; Connecticut Children's Medical Center, Hartford, CT; University of Nebraska Medical Center, Omaha, NE; and Memorial Sloan-Kettering Cancer Center, New York, NY.

Address reprint requests to Sima Jeha, MD, Department of Hematology-Oncology, St Jude Children's Research Hospital, 332 N Lauderdale St, Memphis, TN 38105; e-mail: sima.jeha{at}stjude.org

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

PATIENTS AND 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 3 were febrile neutropenia, anorexia, hypotension, and nausea.

CONCLUSION: 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.

Supported in part by a grant from Genzyme Oncology (successor to ILEX Oncology), San Antonio, TX; also supported in part 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.

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