Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

This is an interventional treatment trial for Adult Acute Megakaryoblastic Leukemia (M7) Read More

Inclusion Criteria:

1. Patients must have histologic evidence of newly diagnosed acute myeloid leukemia (non-M3 AML) as documented by the presence of >20% myeloid blasts in the bone marrow
2. Subjects must be 18 years of age and <= 60
3. Subjects must have an ECOG performance status of 2 or less. (see attachment 1).
4. Subjects must have a life expectancy of at least 4 weeks.
5. Subjects must be able to consume oral medication.
6. Required initial laboratory values: Creatinine 2.0mg/dL; total or direct bilirubin 1.5mg/dL; SGPT(ALT) 3xULN (if not due to the leukemia itself); negative pregnancy test for women with child-bearing potential.
7. Patients must be able to sign consent and be willing and able to comply with scheduled visits, treatment plan and laboratory testing.
8. Subjects must have a left ventricular ejection fraction (LVEF) of >/= 45%.

Exclusion Criteria:

1. Subjects with APL - FAB M3 (t(15;17)(q22;q21)[PML-RAR] are not eligible
2. Subjects must not have received any chemotherapeutic agents for the AML (except Hydroxyurea). Intrathecal ARA-C and intrathecal methotrexate are permissible (as they are not systemic and only isolated to the central nervous system).
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)
   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)
7. Subjects taking fluconazole, voriconazole, itraconazole, posaconazole, and ketoconazole within 72 hours of study entry are not eligible. Reinstitution of fluconazole, voriconazole, itraconazole, posaconazole, ketoconazole and diltiazem is permissible 72 hours after the last dose of sirolimus.
8. Subjects who require HIV protease inhibitors or those with AIDS-related illness
9. Subjects with other severe concurrent disease which in the judgment of the investigator would make the patient inappropriate for entry into this study are ineligible.
10. Subjects must not be pregnant or breastfeeding. Pregnancy tests must be obtained for all females of child-bearing potential. Pregnant or lactating patients are ineligible for this study due to the unknown human fetal or teratogenic toxicities of sirolimus. Males or females of reproductive age may not participate unless they have agreed to use an effective contraceptive method.
11. Subjects who have uncontrolled infection are not eligible. Patients must have any active infections under control. Fungal disease must be stable for at least 2 weeks before study entry.
12. Subjects with bacteremia must have documented negative blood cultures prior to study entry.