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.

Journal Article (Clinical Trial;Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Berg, SL; Blaney, SM; Devidas, M; Lampkin, TA; Murgo, A; Bernstein, M; Billett, A; Kurtzberg, J; Reaman, G; Gaynon, P; Whitlock, J; Krailo, M; Harris, MB; Children's Oncology Group,

Published Date

  • May 20, 2005

Published In

Volume / Issue

  • 23 / 15

Start / End Page

  • 3376 - 3382

PubMed ID

  • 15908649

International Standard Serial Number (ISSN)

  • 0732-183X

Digital Object Identifier (DOI)

  • 10.1200/JCO.2005.03.426


  • eng

Conference Location

  • United States