RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Gene therapy such as augmerosen may make cancer cells more sensitive to chemotherapy drugs. Combining more than one drug with augmerosen may kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of augmerosen plus fludarabine and cytarabine in treating patients who have refractory or relapsed acute myeloid leukemia or acute lymphoblastic leukemia.

OBJECTIVES: I. Determine the maximum tolerated dose of fludarabine and cytarabine when combined with augmerosen (G3139) in patients with refractory or relapsed acute myeloid leukemia or acute lymphoblastic leukemia and recommend a starting dose for phase II studies. II. Determine the qualitative and quantitative toxic effects of this regimen in these patients with regard to organ specificity, time course, predictability, and reversibility. III. Document the therapeutic response in patients treated with this regimen. IV. Measure bcl-2 and related antiapoptotic and proapoptotic proteins in circulating and/or marrow leukemia cells before, during, and after treatment with G3139. V. Measure WT1 expression in leukemic blasts as a surrogate marker for minimal residual disease and correlate it with bcl-2 and related antiapoptotic and proapoptotic gene expression. VI. Determine the time required for bcl-2 levels to recover after treatment with this regimen. VII. 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. VIII. Assess apoptosis in leukemic cells before, during, and after treatment with this regimen. IX. Determine the pharmacokinetics of fludarabine and cytarabine in patients treated with this regimen. X. Perform pharmacodynamic studies of fludarabine and cytarabine on the leukemic cells of patients prior to treatment.

OUTLINE: This is a dose-escalation study of fludarabine and cytarabine. Patients receive augmerosen IV continuously on days 1-10 and filgrastim (G-CSF) subcutaneously beginning on day 5 and continuing until blood counts recover. Patients receive fludarabine IV over 30 minutes followed 3.5 hours later by cytarabine IV over 4 hours on days 6-10. Patients who achieve complete response (CR) receive a second course beginning 4 weeks after completion of the first course. Patients who achieve CR and have a matched sibling or unrelated bone marrow donor may undergo allogeneic bone marrow transplantation. Cohorts of 3-6 patients receive escalating doses of fludarabine and cytarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study.

• Biological: filgrastim
• Biological: oblimersen sodium
• Drug: cytarabine
• Drug: fludarabine phosphate

DISEASE CHARACTERISTICS: Histologically proven refractory or relapsed acute myeloid leukemia or acute lymphoblastic leukemia Marrow cellularity must be at least 20% Must have diagnostic lumbar puncture and treatment with prophylactic intrathecal methotrexate within 1 week prior to entering study No active CNS involvement CNS involvement allowed if no residual leukemic cells are detected in CSF following intrathecal chemotherapy

PATIENT CHARACTERISTICS: Age: 16 and over Performance status: ECOG 0-2 Life expectancy: At least 4 weeks Hematopoietic: See Disease Characteristics Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN)* ALT and AST no greater than 2 times ULN* Alkaline phosphatase no greater than 2 times ULN* * Unless attributable to malignancy Renal: Creatinine no greater than 1.5 mg/dL unless attributable to malignancy Cardiovascular: No symptomatic congestive heart failure No unstable angina pectoris No or cardiac arrhythmia Resting cardiac ejection fraction no less than 45% unless attributable to malignancy Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception before and during study No history of allergy to study medications No uncontrolled concurrent illness No active infection No serious medical or psychiatric illness that would preclude informed consent or limit survival to less than 4 weeks

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics At least 2 weeks since prior chemotherapy except hydroxyurea Endocrine therapy: No concurrent corticosteroids except for grade 4 toxicity unresponsive to all other agents Radiotherapy: At least 4 weeks since prior radiotherapy Surgery: Not specified Other: No other concurrent investigational or standard agents or therapies for leukemia