Azacitidine and Sirolimus in Treating Patients with High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia That Is Relapsed or Refractory 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 clinical diagnosis with prior therapy with azacitidine (Arm C) ** 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 on Arm A as Arm C is closed
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
• 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 radiotherapy (XRT) (small port)
• Patients must have recovered from the toxic effects of any prior chemotherapy to < grade 2 (except for alopecia)
• Creatinine =< 2.0 mg/dL
• Total or direct bilirubin =< 1.5 mg/dL (if not due to the leukemia itself or known Gilbert’s syndrome) (as documented by treating physician)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x upper limit of normal (ULN)
• 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 graft-vs-host disease (GvHD), nor be on any immunosuppression

Exclusion Criteria

• Patients must not be currently receiving any chemotherapy agents (except hydroxyurea) * Intrathecal cytarabine (ARA-C) and intrathecal methotrexate are permissible (as they are not systemic and only isolated to the central nervous system) * Patients cannot 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 hours 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) * Cyclosporine 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 human immunodeficiency virus (HIV) positivity or acquired immunodeficiency syndrome (AIDS)-related illness are not eligible
• Patients with other severe concurrent disease which in the judgment of the investigator would make the patient inappropriate for entry into this study are ineligible
• Patients must not have received any investigational agents within 21 days of study entry
• Patients 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. Males or females of reproductive age may not participate unless they have agreed to use an effective contraceptive method.
• Patients 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. Patients with bacteremia must have documented negative blood cultures prior to study entry