title: Approval summary: nelarabine for the treatment of T-cell lymphoblastic leukemia/lymphoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
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, USA. martin.cohen@fda.hhs.gov
authors.forename: Martin H
authors.initials: MH
authors.lastname: Cohen
authors.forename: John R
authors.initials: JR
authors.lastname: Johnson
authors.forename: Tristan
authors.initials: T
authors.lastname: Massie
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Sridhara
authors.forename: W David
authors.initials: WD
authors.lastname: McGuinn
authors.forename: Sophia
authors.initials: S
authors.lastname: Abraham
authors.forename: Brian P
authors.initials: BP
authors.lastname: Booth
authors.forename: M Anwar
authors.initials: MA
authors.lastname: Goheer
authors.forename: David
authors.initials: D
authors.lastname: Morse
authors.forename: Xiao H
authors.initials: XH
authors.lastname: Chen
authors.forename: Nallaperumal
authors.initials: N
authors.lastname: Chidambaram
authors.forename: Leslie
authors.initials: L
authors.lastname: Kenna
authors.forename: Jogarao V
authors.initials: JV
authors.lastname: Gobburu
authors.forename: Robert
authors.initials: R
authors.lastname: Justice
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000818:Animals; D001087:Arabinonucleosides / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D004285:Dogs; D017277:Drug Approval / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D000882:Haplorhini; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy*; D016399:Lymphoma, T-Cell / Q000188:drug therapy*; D008657:Metabolic Clearance Rate; D051379:Mice; D008954:Models, Biological; D011817:Rabbits; D051381:Rats; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D001087:Arabinonucleosides; C104457:nelarabine