title: Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434.
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.
  
  
  METHODS
  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.
authors.affiliation: University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
authors.forename: Stuart S
authors.initials: SS
authors.lastname: Winter
authors.affiliation: University of Virginia Children's Hospital, Charlottesville, Virginia.
authors.forename: Kimberly P
authors.initials: KP
authors.lastname: Dunsmore
authors.affiliation: Biostatistics, the University of Florida, Gainesville, Florida.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.affiliation: University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
authors.forename: Nancy
authors.initials: N
authors.lastname: Eisenberg
authors.affiliation: University of Rochester, Rochester, New York.
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Asselin
authors.affiliation: Seattle Children's Hospital, Seattle, Western Australia.
authors.forename: Brent L
authors.initials: BL
authors.lastname: Wood
authors.affiliation: C S Mott Children's Hospital, Ann Arbor, Michigan.
authors.forename: Marcia S
authors.initials: MS
authors.lastname: Leonard Rn
authors.affiliation: Princess Margaret Hospital for Children, Perth, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Murphy
authors.affiliation: Nationwide Children's Hospital, Columbus, Ohio.|Ohio State University, Columbus, Ohio.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Gastier-Foster
authors.affiliation: University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carroll
authors.affiliation: Ohio State University, Columbus, Ohio.
authors.forename: Nyla A
authors.initials: NA
authors.lastname: Heerema
authors.affiliation: UCSF Medical Center - Parnassus, San Francisco, California.
authors.forename: Mignon L
authors.initials: ML
authors.lastname: Loh
authors.affiliation: University of Utah, Primary Children's Hospita, Salt Lake City.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Raetz
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Winick
authors.affiliation: Perlmutter Cancer Center, New York University Langone Medical Center, New York, New York.
authors.forename: William L
authors.initials: WL
authors.lastname: Carroll
authors.affiliation: University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunger
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001087:Arabinonucleosides; D001215:Asparaginase; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D008727:Methotrexate; D009367:Neoplasm Staging; D011092:Polyethylene Glycols; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D001087:Arabinonucleosides; D011092:Polyethylene Glycols; C104457:nelarabine; C042705:pegaspargase; D001215:Asparaginase; D008727:Methotrexate
keywords: BFM chemotherapy regimen; T-ALL; nelarabine