title: Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children's Oncology Group.
abstract: OBJECTIVE
  Nelarabine (compound 506U78), a water soluble prodrug of 9-b-d-arabinofuranosylguanine, is converted to ara-GTP in T lymphoblasts. We sought to define the response rate of nelarabine in children and young adults with refractory or recurrent T-cell disease.
  
  
  METHODS
  We performed a phase II study with patients stratified as follows: stratum 1: > or = 25% bone marrow blasts in first relapse; stratum 2: > or = 25% bone marrow blasts in > or = second relapse; stratum 3: positive CSF; stratum 4: extramedullary (non-CNS) relapse. The initial nelarabine dose was 1.2 g/m2 daily for 5 consecutive days every 3 weeks. There were two dose de-escalations due to neurotoxicity on this or other studies. The final dose was 650 mg/m2/d for strata 1 and two patients and 400 mg/m2/d for strata 3 and four patients.
  
  
  RESULTS
  We enrolled 121 patients (106 assessable for response) at the final dose levels. Complete plus partial response rates at the final dose levels were: 55% in stratum 1; 27% in stratum 2; 33% in stratum 3; and 14% in stratum 4. There were 31 episodes of > or = grade 3 neurologic adverse events in 27 patients (18% of patients).
  
  
  CONCLUSIONS
  Nelarabine is active as a single agent in recurrent T-cell leukemia, with a response rate more than 50% in first bone marrow relapse. The most significant adverse events associated with nelarabine administration are neurologic. Further studies are planned to determine whether the addition of nelarabine to front-line therapy for T-cell leukemia in children will improve survival.
authors.affiliation: Texas Children's Cancer Center, Baylor College of Medicine, 6621 Fannin St, MC3-3320, Houston, TX 77030, USA. sberg@txccc.org
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Berg
authors.forename: Susan M
authors.initials: SM
authors.lastname: Blaney
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.forename: Tom A
authors.initials: TA
authors.lastname: Lampkin
authors.forename: Anthony
authors.initials: A
authors.lastname: Murgo
authors.forename: Mark
authors.initials: M
authors.lastname: Bernstein
authors.forename: Amy
authors.initials: A
authors.lastname: Billett
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
authors.forename: Greg
authors.initials: G
authors.lastname: Reaman
authors.forename: Paul
authors.initials: P
authors.lastname: Gaynon
authors.forename: James
authors.initials: J
authors.lastname: Whitlock
authors.forename: Mark
authors.initials: M
authors.lastname: Krailo
authors.forename: Michael B
authors.initials: MB
authors.lastname: Harris
mesh_terms: D000293:Adolescent; D000328:Adult; D001087:Arabinonucleosides / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology*; D008297:Male; D020714:Maximum Tolerated Dose; D009367:Neoplasm Staging; D012008:Recurrence; D018570:Risk Assessment; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D001087:Arabinonucleosides; C104457:nelarabine