Sirolimus in Combination With MEC in High Risk Myeloid Leukemias

A Prospective Single Institution Pilot Study Evaluating the Pharmacokinetics of Sirolimus in Combination With MEC (Mitoxantrone + Etoposide + Cytarabine) in Patients With High Risk Leukemias

The purpose of this study is to evaluate the side effects of sirolimus (rapamycin) given in combination with chemotherapy (Mitoxantrone + Etoposide + Cytarabine (MEC)) on high risk myeloid leukemias.

Inclusion Criteria:

• Must have histologic evidence of advanced myeloid leukemias defined as one of the following: primary refractory non-M3 AML; relapsed non-M3 AML; secondary AML; intermediate or poor prognosis de novo AML in patients who are >= 60 years old
• >= 18 years of age
• ECOG performance status of 0, 1
• Able to consume oral medication
• Initial laboratory values: creatinine <= 2.0 mg/dL; total or direct bilirubin <= 1.5/dL; SGPT(ALT) <= 3xULN; negative pregnancy test for women with child-bearing potential
• Ejection fraction of >= 45%

Exclusion Criteria:

• Subjects with FAM B3
• Must not be receiving chemotherapy (except Hydroxyurea)
• Not receiving growth factors, except for erythropoietin
• Subjects with a "currently active" second malignancy other than non-melanoma skin cancers
• Subjects with uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure, MI within the last 6 months or uncontrolled cardiac arrhythmia
• Subjects taking diltiazem
• Subjects who require HIV protease inhibitors or those with AIDS-related illnesses
• No evidence of cerebellar dysfunction at baseline or during prior cytarabine therapy
• Not pregnant or breastfeeding
• Uncontrolled infection
• Subjects taking Carbamazepine, Rifabutin, Rifampin, Rifapentine, St. John's wort, Clarithromycin, Cyclosporine, Diltiazem, Erythromycin, Telithromycin, Verapamil, Tacrolimus