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Clin Lymphoma Myeloma Leuk. 2013 Oct;13(5):559-67. doi: 10.1016/j.clml.2013.03.019. Epub 2013 Jun 10.

Phase I study assessing the safety and tolerability of barasertib (AZD1152) with low-dose cytosine arabinoside in elderly patients with AML.

Author information

1
MD Anderson Cancer Center, The University of Texas, Houston, TX. Electronic address: hkantarjian@mdanderson.org.

Abstract

INTRODUCTION:

Barasertib is the pro-drug of barasertib-hydroxy-quinazoline pyrazole anilide, a selective Aurora B kinase inhibitor that has demonstrated preliminary anti-AML activity in the clinical setting.

PATIENTS AND METHODS:

This Phase I dose-escalation study evaluated the safety and tolerability of barasertib, combined with LDAC, in patients aged 60 years or older with de novo or secondary AML. Barasertib (7-day continuous intravenous infusion) plus LDAC 20 mg (subcutaneous injection twice daily for 10 days) was administered in 28-day cycles. The MTD was defined as the highest dose at which ≤ 1 patient within a cohort of 6 experienced a dose-limiting toxicity (DLT) (clinically significant adverse event [AE] or laboratory abnormality considered related to barasertib). The MTD cohort was expanded to 12 patients.

RESULTS:

Twenty-two patients (median age, 71 years) received ≥ 1 treatment cycle (n = 6, 800 mg; n = 13, 1000 mg; n = 3, 1200 mg). DLTs were reported in 2 patients (both, National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 stomatitis/mucositis; 1200 mg cohort). The most common AEs were infection (73%), febrile neutropenia (59%), nausea (50%), and diarrhea (46%). Barasertib plus LDAC resulted in an overall response rate (International Working Group criteria) of 45% (n = 10/22; according to investigator opinion).

CONCLUSION:

The MTD of 1000 mg barasertib in combination with LDAC in older patients with AML was associated with acceptable tolerability and preliminary anti-AML activity.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00926731.

KEYWORDS:

Acute myeloid leukemia; Barasertib-hQPA; Dose-escalation study

PMID:
23763917
PMCID:
PMC3775947
DOI:
10.1016/j.clml.2013.03.019
[Indexed for MEDLINE]
Free PMC Article

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