12th Congress of the European Hematology ... - Haematologica

12 th Congress of the European Hematology Association
of the level of DNA damage repair proteins DNA-PKcs, Ku70 and Ku80.
Post-dose blood and bone marrow aspirate samples were obtained from
a subset of patients to determine sensitivity to SNS-595 ex vivo as well
as evidence for DNA damage, apoptosis, and cell-cycle response. H2AX
phosphorylation, PARP cleavage, and G2 arrest were evaluated. Results.
21 patients (Arm A) and 14 patients (Arm B) were evaluable. All patients
were consented and had refractory and/or relapsed disease (median 3
prior regimens (range 1-6)). Accrual and dose-escalation have continued
at 60 mg/m 2 for Arm A and 30 mg/m 2 for Arm B. Diagnoses: AML 32
patients, ALL 3 patients. One dose-limiting toxicity, prolonged neutropenia,
was observed. Non-dose limiting adverse events included
nausea/vomiting, diarrhea, and mucositis; grade 4 neutropenic fever
was observed in only 1 patient. SNS-595 PK were dose proportional
(dose range characterized: 9-50 mg/m 2 ) and volume of distribution and
clearance values were unchanged across the dose range. Evidence of
DNA damage was observed in patients treated with