Objectives: 1 To determine the maximal tolerable dose of fludarabine and ARA-C in combination with G3139 in patients with relapsed or refractory acute leukemia [acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)] and to recommend a starting dose for Phase II studies of this combination of agents in this patient population. 2. To define the qualitative and quantitative toxicities of these combinations of agents in regard to organ specificity, time course, predictability, and reversibility. 3. To document the therapeutic response of these combinations of agents in patients with refractory or relapsed acute leukemia. 4. To measure BCL-2 and related antiapoptotic and proapoptotic proteins in circulating and/or marrow leukemia cells before, during and after treatment with 139. 5. To measure WT1 expression in leukemic blasts as a surrogate marker for minimal residual disease and to correlate it with BCL2 and related antiapoptotic and proapoptotic gene expression. 6. To determine the time required for BCL-2 levels to recover after combined treatment with G3139 and FLAG. 7. To determine if TP53 mutations are present in leukemic blasts and how these mutations may affect expression of BAX, level of treatment-induced apoptosis, and clinical Endpoints. 8. To assess apoptosis in leukemic cells before, during and after combined treatment with G3139, fludarabine and ARA-C. 9. To evaluate the pharmacokinetics of fludarabine and ARA-C in patients receiving this combination of agents. 10. To perform pharmacodynamic studies of fludarabine and ARA-C on the leukemic cells of patients prior to treatment.
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