FDA drug approval summary: nelarabine (Arranon) for the treatment of T-cell lymphoblastic leukemia/lymphoma.
OBJECTIVE
To describe the clinical trials leading to U.S. Food and Drug Administration (FDA) approval of nelarabine (Arranon), a new purine analogue, for the treatment of patients with T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens.


METHODS
Two phase II trials, one conducted in pediatric patients and the other in adult patients, were reviewed. Patients were in their first or subsequent relapse and/or were refractory to first-line therapy. The dose and schedule of i.v. nelarabine in the pediatric and adult studies were 650 mg/m2 per day daily for 5 days and 1,500 mg/m2 i.v. on days 1, 3, and 5, respectively. Treatments were repeated every 21 days. Study endpoints 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 after, or had been refractory to, two or more induction regimens. CR to nelarabine treatment was observed in five patients (13%) and CR+CR* was observed in nine patients (23%). The adult efficacy population consisted of 28 patients. CR to nelarabine treatment was observed in five patients (18%) and CR+CR* was observed in six patients (21%). Neurologic toxicity was dose limiting for both pediatric and adult patients. Other severe toxicities included hematologic, hepatic, and metabolic laboratory abnormalities in pediatric patients and gastrointestinal and pulmonary toxicities in adults.


CONCLUSIONS
On October 28, 2005, the FDA granted accelerated approval for nelarabine for treatment of patients with relapsed or refractory T-ALL/T-LBL after at least two prior regimens. This use is based on the induction of CR. The applicant will conduct postmarketing clinical trials to demonstrate clinical benefit, for example, survival prolongation.
Cohen
Martin H
MH
Division of Oncology Drug Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Rockville, MD, USA. martin.cohen@fda.hhs.gov
Johnson
John R
JR
Justice
Robert
R
Pazdur
Richard
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D001087:Arabinonucleosides / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D017322:Clinical Trials, Phase II as Topic; D017277:Drug Approval / Q000331:legislation & jurisprudence*; D006801:Humans; D007223:Infant; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy*; D008875:Middle Aged; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D014481:United States; D014486:United States Food and Drug Administration
D001087:Arabinonucleosides; C104457:nelarabine