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

1. 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.

2. Patients must be ≥ 18 years old

3. Patients must have an ECOG performance status of \<= 2 (see Attachment 1).

4. Patients must have a life expectancy of at least 4 weeks.

5. Patients must be able to consume oral medication.

6. Patients must have completed any radiotherapy four weeks prior to study entry, 0-2 weeks for local palliative XRT (small port).

7. Patients must have recovered from the toxic effects of any prior chemotherapy to \< Grade 2 (except for alopecia).

8. 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.

9. Patients must be able to sign consent and be willing and able to comply with scheduled visits, treatment plan and laboratory testing.

10. Patients may have had a prior stem cell transplant (autologous or allogeneic), however they may not have active GvHD, nor be on any immunosuppression

* 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.

What this study is about