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Clinical Trial
. 2018 Mar 15;124(6):1150-1159.
doi: 10.1002/cncr.31099. Epub 2017 Dec 19.

Toxicity associated with intensive postinduction therapy incorporating clofarabine in the very high-risk stratum of patients with newly diagnosed high-risk B-lymphoblastic leukemia: A report from the Children's Oncology Group study AALL1131

Wanda L Salzer  1 , Michael J Burke  2 , Meenakshi Devidas  3 , Si Chen  3 , Lia Gore  4 , Eric C Larsen  5 , Michael Borowitz  6 , Brent Wood  7 , Nyla A Heerema  8 , Andrew J Carroll  9 , Joanne M Hilden  10   11 , Mignon L Loh  12 , Elizabeth A Raetz  13 , Naomi J Winick  14 , William L Carroll  15 , Stephen P Hunger  16
Affiliations
Clinical Trial

Toxicity associated with intensive postinduction therapy incorporating clofarabine in the very high-risk stratum of patients with newly diagnosed high-risk B-lymphoblastic leukemia: A report from the Children's Oncology Group study AALL1131

Wanda L Salzer et al. Cancer. .

Erratum in

Abstract

Background: Children, adolescents, and young adults with very high-risk (VHR) B acute lymphoblastic leukemia (B-ALL) have poor outcomes, and novel therapies are needed for this subgroup. The AALL1131 study evaluated postinduction therapy using cyclophosphamide (CPM), etoposide (ETOP), and clofarabine (CLOF) for patients with VHR B-ALL.

Methods: Patients who were 1 to 30 years old and had VHR B-ALL received modified Berlin-Frankfurt-Münster therapy after induction and were randomized to 1) CPM, cytarabine, mercaptopurine, vincristine (VCR), and pegaspargase (control arm), 2) CPM, ETOP, VCR, and pegaspargase (experimental arm 1), or 3) CPM, ETOP, CLOF (30 mg/m2 /d × 5), VCR, and pegaspargase (experimental arm 2) during the second half of consolidation and delayed intensification.

Results: The rates of grade 4/5 infections and grade 3/4 pancreatitis were significantly increased in experimental arm 2. The dose of CLOF was, therefore, reduced to 20 mg/m2 /d × 5, and myeloid growth factor was required after CLOF administration. Despite these changes, 4 of 39 patients (10.3%) developed grade 4 infections, with 1 of these patients developing a grade 5 acute kidney injury attributed to CLOF, whereas only 1 of 46 patients (2.2%) in experimental arm 1 developed grade 4 infections, and there were no grade 4/5 infections in the control arm (n = 20). Four patients in experimental arm 2 had prolonged cytopenias for >60 days, whereas none did in the control arm or experimental arm 1. Counts failed to recover for 2 of these patients, one having a grade 5 acute kidney injury and the other removed from protocol therapy; both events occurred 92 days after the start of consolidation part 2.

Conclusions: In AALL1131, CLOF, administered with CPM and ETOP, was associated with unacceptable toxicity. Cancer 2018;124:1150-9. © 2017 American Cancer Society.

Keywords: acute; childhood; clofarabine; lymphoblastic leukemia; toxicity.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1. Pre-Amendment Clofarabine 30 mg/m2/day × 5 Consort diagram
Between 2/27/2012 and 9/13/2012 (only including eligible patients)
Figure 2
Figure 2. Post-Amendment Clofarabine 20 mg/m2/day × 5 Consort diagram
Between 11/25/2013 and 5/5/2014 (only including eligible patients)
See this image and copyright information in PMC

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