Veliparib and Temozolomide in Treating Patients With Acute Leukemia

PRIMARY OBJECTIVES: I. To define the maximum-tolerated dose (MTD) and recommended phase II dose of ABT-888 (veliparib) administered in combination with temozolomide in patients with acute leukemias. II. To evaluate the feasibility, safety, and toxicity of administering ABT-888 in combination with temozolomide in patients with acute leukemias. SECONDARY OBJECTIVES: I. To document response in acute leukemias. II. To observe the pharmacokinetics of both ABT-888 and temozolomide when administered alone and in combination. III. To study the pharmacodynamics to determine the levels of poly(ADP-ribose) (PAR) before and after administration of ABT-888 and temozolomide in patient leukemia blasts, to analyze methyl-guanine methyl-transferase (MGMT) protein levels in primary leukemia blasts, and to quantify the induction of gamma-H2A histone family, member X (y-H2AX) and RAD51 recombinase (RAD51) foci in patient leukemia blasts after treatment. OUTLINE: This is a dose-escalation study of veliparib. Patients receive veliparib orally (PO) once daily (QD) on day 1 and twice daily on days 4-12 and temozolomide PO QD on days 3-9 of course 1. Beginning at least 30 days after the start of treatment, patients receive veliparib PO twice daily (BID) on days 1-8 and temozolomide PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving complete remission receive 5 more courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days.