3-ap and high-dose cytarabine in treating patients with advanced hematologic malignancies

Conditions: Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia

Summary: drugs used in chemotherapy, such as cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. 3-ap may help cytarabine kill more cancer cells by making them more sensitive to the drug. this phase i trial is studying the side effects and best dose of 3-ap when given with high-dose cytarabine in treating patients with advanced hematologic malignancies

primary objectives: i. determine the maximum tolerated dose of 3-ap (triapine) administered with high-dose cytarabine in patients with advanced hematologic malignancies. secondary objectives: i. determine the clinical activity of this regimen in these patients. ii. determine the effect of treatment with 3-ap (triapine) on intracellular levels of cytarabine in these patients. outline: this is a dose-escalation study of 3-ap (triapine). patients receive high-dose cytarabine iv over 2 hours on days 1-5 and 3-ap (triapine) iv over 2 hours on days 2-5. treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients in each stratum receive escalating doses of 3-ap (triapine) until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. patients are followed for up to 2 years. projected accrual: a total of 6-48 patients (3-24 per stratum) will be accrued for this study within 15-24 months.

Eligibility criteria:
inclusion criteria: * histologically confirmed diagnosis of 1 of the following hematologic malignancies: * relapsed or refractory acute myeloid leukemia (aml) * relapsed or refractory acute lymphoblastic leukemia * secondary aml, including aml arising from antecedent hematologic diseases, such as myelodysplastic syndromes or myeloproliferative disorders or therapy-related aml * chronic myeloid leukemia in accelerated or blast phase * refractory to standard therapy or no standard therapy exists * no known brain metastases * performance status - calgb 0-2 * performance status - karnofsky 60-100% * no g6pd deficiency * bilirubin \< 2.0 mg/dl (unless due to gilbert's syndrome) * ast and alt \< 2.5 times upper limit of normal (uln) * creatinine \< 1.5 times uln * no symptomatic congestive heart failure * no unstable angina pectoris * no cardiac arrhythmia * no pulmonary disease requiring oxygen * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no prior allergic reactions attributed to compounds of similar chemical or biological composition to study drugs * no neuropathy * no ongoing or active infection * no psychiatric illness or social situation that would preclude study compliance * no other concurrent uncontrolled illness * no concurrent biologic agents * at least 72 hours since prior hydroxyurea * at least 2 weeks since other prior chemotherapy (6 weeks for mitomycin or nitrosoureas) * no other concurrent chemotherapy * at least 2 weeks since prior radiotherapy * no concurrent radiotherapy * recovered from all prior therapy * at least 4 weeks since prior investigational agents * no other concurrent investigational therapy * no other concurrent anticancer therapy * no concurrent combination antiretroviral therapy for hiv-positive patients