Inclusion Criteria:
1. Patients must have histologic evidence of high risk acute myeloid leukemia defined as one of the following:
1. Primary refractory non-M3 AML
* Residual leukemia after a minimum of 2 prior courses of chemotherapy (Same or different)
* Evidence of leukemia recurrence after a nadir bone marrow biopsy demonstrates no evidence of residual leukemia.
* Evidence of leukemia after induction therapy which, in the opinion of the investigator, would be appropriate for reinduction with sirolimus/MEC therapy.
2. Relapsed non-M3 AML
3. Previously untreated non-M3 AML age \>60 with no evidence of favorable karyotype defined by presence of t(8;21)(q22;q22) \[AML1-ETO\], inv16(p13;q22), or t(16;16)(p13;q22) \[CBFβ;MYH11\] by cytogenetics, FISH, or RT-PCR
4. Previously untreated secondary AML (from antecedent hematologic malignancy or following therapy with radiation or chemotherapy for another disease) with no evidence of favorable karyotype defined by presence of t(8;21)(q22;q22) \[AML1-ETO\], inv16(p13;q22), or t(16;16)(p13;q22) \[CBFβ;MYH11\] by cytogenetics, FISH, or RT-PCR
2. Subjects must be ≥ 18 years of age.
3. Subjects must have an ECOG performance status of 2 or less (see Appendix1).
4. Subjects must have a life expectancy of at least 4 weeks.
5. Subjects must be able to consume oral medication.
6. Subjects must have recovered from the toxic effects of any prior chemotherapy to =\< Grade 1 (except alopecia).
7. Required initial laboratory values:
1. Creatinine ≤ 2.0mg/dL
2. total or direct bilirubin ≤ 1.5mg/dL; SGPT (ALT) ≤ 3xULN
3. negative pregnancy test for women with child-bearing potential.
8. Patients must be able to sign consent and be willing and able to comply with scheduled visits, treatment plan and laboratory testing.
9. Subjects must have a left ventricular ejection fraction (LVEF) of ≥ 45%.
Exclusion Criteria:
1. Subjects with FAB M3 (t (15; 17) (q22; q21) \[PML-RARα\]) are not eligible.
2. Subjects must not be receiving any chemotherapy agents (except Hydroxyurea).
a) Intrathecal methotrexate and cytarabine are permissible.
3. Subjects must not be receiving growth factors, except for erythropoietin.
4. Subjects with a "currently active" second malignancy, other than non-melanoma skin cancers are not eligible.
5. Subjects with uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure, myocardial infarction within the past 6 months or serious uncontrolled cardiac arrhythmia are not eligible.
6. Subjects taking the following are not eligible:
1. Carbamazepine (e.g., Tegretol)
2. Rifabutin (e.g., Mycobutin) or
3. Rifampin (e.g., Rifadin)
4. Rifapentine (e.g., Priftin)
5. St. John's wort
6. Clarithromycin (e.g., Biaxin)
7. Cyclosporine (e.g. Neoral or Sandimmune)
8. Diltiazem (e.g., Cardizem)
9. Erythromycin (e.g., Akne-Mycin, Ery-Tab)
10. Itraconazole (e.g., Sporanox)
11. Ketoconazole (e.g., Nizoral)
12. Telithromycin (e.g., Ketek)
13. Verapamil (e.g., Calan SR, Isoptin, Verelan)
14. Voriconazole (e.g., VFEND)
15. Tacrolimus (e.g. Prograf) Subjects taking fluconozole, voriconizole, itraconazole, posaconazole, and ketokonazole within 72 hours of study drug starting are not eligible. Reinstitution of fluconozole, voriconizole, itraconazole, posaconazole, ketokonazole and diltiazem is permissible 72 hours after the last dose of sirolimus.
