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Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. doi: 10.1002/pbc.25470. Epub 2015 Mar 8.

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

Author information

1
University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
2
University of Virginia Children's Hospital, Charlottesville, Virginia.
3
Biostatistics, the University of Florida, Gainesville, Florida.
4
University of Rochester, Rochester, New York.
5
Seattle Children's Hospital, Seattle, Western Australia.
6
C S Mott Children's Hospital, Ann Arbor, Michigan.
7
Princess Margaret Hospital for Children, Perth, Australia.
8
Nationwide Children's Hospital, Columbus, Ohio.
9
Ohio State University, Columbus, Ohio.
10
University of Alabama at Birmingham, Birmingham, Alabama.
11
UCSF Medical Center - Parnassus, San Francisco, California.
12
University of Utah, Primary Children's Hospita, Salt Lake City.
13
University of Texas Southwestern Medical Center, Dallas, Texas.
14
Perlmutter Cancer Center, New York University Langone Medical Center, New York, New York.
15
University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado.

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.

KEYWORDS:

BFM chemotherapy regimen; T-ALL; nelarabine

PMID:
25755211
PMCID:
PMC4433576
DOI:
10.1002/pbc.25470
[Indexed for MEDLINE]
Free PMC Article

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