Sirolimus and Azacitidine in Treating Patients With High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia That is Recurrent or Not Eligible for Intensive Chemotherapy

Inclusion Criteria

• Patients must have a diagnosis of one of the following:
• MDS (Arm A): High-risk MDS defined as: >5% blasts in bone marrow and/or the following cytogenetic categories: presence of inv(3)/t(3q)/del(3q), -7/del(7q), complex cytogenetics (3 or more abnormalities)
• AML (Arm B): Relapsed/refractory/unable to tolerate conventional chemotherapy
• MDS or AML as above BUT with prior therapy with Azacitibine (Arm C): Patients who meet criteria for either Arm A or Arm B but have been treated or are currently treated with Azacitibine *Note: As of July 2018, only high risk MDS patients will be eligible as Arm B is closed. As of October 2017, those patients with MDS who have received prior treatment will now be enrolled in Arm A as Arm C is closed.
• Patients must be ≥ 18 years old
• Patients must have an ECOG performance status of <= 2 (see Attachment 1).
• Patients must have a life expectancy of at least 4 weeks.
• Patients must be able to consume oral medication.
• Patients must have completed any radiotherapy four weeks prior to study entry, 0-2 weeks for local palliative XRT (small port).
• Patients must have recovered from the toxic effects of any prior chemotherapy to < Grade 2 (except for alopecia).
• Required initial laboratory values: Creatinine≤ 2.0mg/dL; total or direct bilirubin ≤ 1.5mg/dL (if not due to the leukemia itself or known Gilbert's Syndrome);(as documented by treating physician) SGPT(ALT) ≤ 3xULN; glucose <200 mg/dL, negative pregnancy test for women of child-bearing potential.
• Patients must be able to sign consent and be willing and able to comply with scheduled visits, treatment plan and laboratory testing.
• Patients may have had a prior stem cell transplant (autologous or allogeneic), however they may not have active GvHD, nor be on any immunosuppression

Exclusion Criteria

• Patients must not be receiving any chemotherapy agents (except Hydroxyurea)
• Intrathecal ARA-C and intrathecal methotrexate are permissible (as they are not systemic and only isolated to the central nervous system).
• Patients can not have received more than 3 prior lines of therapy for their hematologic malignancy. Patient may have previously had azacitidine or decitabine will be eligible to enroll on Arm A (MDS)
• Patients must not be receiving growth factors.
• Patients with a current second malignancy requiring systemic therapy, other than non-melanoma skin cancers, are not eligible. If a patient has had a prior second malignancy that is not currently requiring active treatment, the patient will be considered eligible.
• Patients 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.
• Patients may not take any of the following medications while on study, but will be considered eligible if medication is discontinued 72 hrs prior to first dose of Sirolimus:
• Carbamazepine (e.g. Tegretol)
• Rifabutin (e.g. Mycobutin)
• Rifampin (e.g. Rifadin)
• Rifapentine (e.g. Priftin)
• St. John's Wort- may decrease effects of sirolimus by decreasing the amount of sirolimus in the body
• Clarithromycin (e.g. Biaxin)
• Cyclosporin e.g. (Neoral or Sandimmune)
• Diltiazem (e.g. Cardizem)
• Erythromycin (e.g. Akne-Mycin, Ery-Tab)
• Itraconazole (e.g. Sporanox)
• Fluconazole (e.g. Diflucan)
• Ketoconazole (e.g. Nizoral)
• Telithromycin (e.g. Ketek)
• Verapamil (e.g. Calan SR, Isoptin, Verelan)
• Voriconazole (e.g. VFEND) - May increase the effects of sirolimus by increasing the amount of this medicine in the body. Can take 72 hours after last dose of Sirolimus
• Tacrolimus (e.g. Prograf) - May cause liver transplant rejection or serious side effects in patients on sirolimus.
• Patients with known HIV positivity or AIDS-related illness are not eligible.
• Patients with other severe concurrent disease which in the judgment of the investigator would make the patient