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

J Clin Oncol. 2005 May 20;23(15):3376-82. doi: 10.1200/JCO.2005.03.426.


Purpose: 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.

Patients and 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).

Conclusion: 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II

MeSH terms

  • Adolescent
  • Adult
  • Arabinonucleosides / administration & dosage*
  • Arabinonucleosides / adverse effects
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Infusions, Intravenous
  • Leukemia, T-Cell / drug therapy*
  • Leukemia, T-Cell / mortality*
  • Leukemia, T-Cell / pathology*
  • Male
  • Maximum Tolerated Dose
  • Neoplasm Staging
  • Recurrence
  • Risk Assessment
  • Survival Rate
  • Treatment Outcome


  • Arabinonucleosides
  • nelarabine