This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cohen, M. H. Articles by Pazdur, R. Search for Related Content PubMed PubMed Citation Articles by Cohen, M. H. Articles by Pazdur, R.

Approval Summary: Nelarabine for the Treatment of T-Cell Lymphoblastic Leukemia/Lymphoma

Authors' Affiliation: Division of Drug Oncology Products, Office of Oncology Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland

Requests for reprints: Martin H. Cohen, Division of Drug Oncology Products, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857. Phone: 301-594-5740; Fax: 301-594-0499; E-mail: martin.cohen{at}fda.hhs.gov.

Purpose: To describe the clinical studies, chemistry manufacturing and controls, and clinical pharmacology and toxicology that led to Food and Drug Administration approval of nelarabine (Arranon) for the treatment of T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma.

Experimental Design: Two phase 2 trials, one conducted in pediatric patients and the other in adult patients, were reviewed. The i.v. dose and schedule of nelarabine in the pediatric and adult studies was 650 mg/m²/d daily for 5 days and 1,500 mg/m² on days 1, 3, and 5, respectively. Treatments were repeated every 21 days. Study end points were the rates of complete response (CR) and CR with incomplete hematologic or bone marrow recovery (CR*).

Results: The pediatric efficacy population consisted of 39 patients who had relapsed or had been refractory to two or more induction regimens. CR to nelarabine treatment was observed in 5 (13%) patients and CR+CR* was observed in 9 (23%) patients. The adult efficacy population consisted of 28 patients. CR to nelarabine treatment was observed in 5 (18%) patients and CR+CR* was observed in 6 (21%) patients. Neurologic toxicity was dose limiting for both pediatric and adult patients. Other severe toxicities included laboratory abnormalities in pediatric patients and gastrointestinal and pulmonary toxicities in adults.

Conclusions: On October 28, 2005, the Food and Drug Administration granted accelerated approval for nelarabine for treatment of patients with relapsed or refractory T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma after at least two prior regimens. This use is based on the induction of CRs. The applicant will conduct postmarketing clinical trials to show clinical benefit (e.g., survival prolongation).

This article has been cited by other articles:

				V. Gandhi, C. Tam, S. O'Brien, R. C. Jewell, C. O. Rodriguez Jr, S. Lerner, W. Plunkett, and M. J. Keating Phase I Trial of Nelarabine in Indolent Leukemias J. Clin. Oncol., March 1, 2008; 26(7): 1098 - 1105. [Abstract] [Full Text] [PDF]

				S. S. Winter, Z. Jiang, H. M. Khawaja, T. Griffin, M. Devidas, B. L. Asselin, and R. S. Larson Identification of genomic classifiers that distinguish induction failure in T-lineage acute lymphoblastic leukemia: a report from the Children's Oncology Group Blood, September 1, 2007; 110(5): 1429 - 1438. [Abstract] [Full Text] [PDF]