Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology group Study AALL0434

Stuart S. Winter, Kimberly P. Dunsmore, Meenakshi Devidas, Nancy Eisenberg, Barbara L. Asselin, Brent L. Wood, Marcia S. Leonard Rn, John Murphy, Julie M. Gastier-Foster, Andrew J. Carroll, Nyla A. Heerema, Mignon L. Loh, Elizabeth A. Raetz, Naomi J. Winick, William L. Carroll, Stephen P. Hunger

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Background: Nelarabine has shown impressive single agent clinical activity in T-cell acute lymphoblastic leukemia (T-ALL), but has been associated with significant neurotoxicities in heavily pre-treated patients. We showed previously that it was safe to add nelarabine to a BFM-86 chemotherapy backbone (AALL00P2). Children's Oncology Group (COG) AALL0434 is a Phase III study designed to test the safety and efficacy of nelarabine when incorporated into a COG augmented BFM-based regimen, which increases exposure to agents with potential neurotoxicity compared to the historical AALL00P2 regimen. Procedure: AALL0434 included a safety phase to assess nelarabine toxicity. Patients with high-risk (HR) T-ALL were randomized to receive Capizzi-style escalating methotrexate (MTX) plus pegaspargase or high dose (HD) MTX with/without six five-days courses of nelarabine. We report results from 94 patients who participated in the initial safety phase of the study. Results: There were no differences in the incidence of peripheral motor neuropathies, sensory neuropathies or central neurotoxicities among those randomized to the nelarabine (n = 47) and non-nelarabine arms (n = 47). Conclusions: The addition of nelarabine to COG-augmented BFM chemotherapy regimen is safe and feasible. The ongoing AALL0434 Efficacy Phase will determine whether the addition of nelarabine treatment improves outcome for patients with T-ALL. Pediatr Blood Cancer 2015;62:1176-1183.

Original languageEnglish (US)
Pages (from-to)1176-1183
Number of pages8
JournalPediatric Blood and Cancer
Volume62
Issue number7
DOIs
StatePublished - Jul 1 2015

Keywords

  • BFM chemotherapy regimen
  • Nelarabine
  • T-ALL

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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