Phase II study of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia.

Abstract

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 > or = 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.

• Authors: 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 24 Issue 12 Pg. 1917-23 (Apr 20 2006) ISSN: 1527-7755 [Electronic] United States
• PMID: 16622268 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adenine Nucleotides
• Arabinonucleosides
• Clofarabine

Topics

• Adenine Nucleotides
• Adolescent
• Adult
• Arabinonucleosides (administration & dosage, adverse effects, therapeutic use)
• Child
• Child, Preschool
• Clofarabine
• Female
• Humans
• Infant
• Infusions, Intravenous
• Male
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, pathology)
• Recurrence
• Treatment Outcome