Pembrolizumab and Decitabine for Refractory or Relapsed Acute Myeloid Leukemia

* INCLUSION CRITERIA:
* Unequivocal diagnosis of relapsed or refractory acute myeloid leukemia (AML) confirmed by an NIH attending pathologist within 30 days of study enrollment (includes residual AML as confirmed by institutional standards by NIH pathologists
* Received at least one prior AML therapy before study enrollment.
* Ability to comprehend the investigational nature of the study and provide informed consent.
* Be at least 18 years of age on day of signing informed consent.
* Availability of a physician willing to assume clinical care after completion of the study.
* Be willing to provide blood and bone marrow for research as described in the study.
* Have a performance status of less than or equal to 1 on the ECOG Performance Scale
* Demonstrate adequate organ function as defined below, all screening labs should be performed within 14 days of treatment initiation.
* Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
* Female subjects of childbearing potential must be willing to use an adequate method of contraception; Contraception, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
* Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
* Adequate Organ Function Laboratory Values: System Laboratory - Value

  * Renal

    ---Serum Creatinine - Less than or equal to 1.5 X upper limit of normal (ULN)
  * Hepatic

    * Serum total bilirubin Less than or equal to 1.5 X ULN OR
    * Direct bilirubin less than or equal to ULN for subjects with total bilirubin levels greater than 1.5 ULN
    * AST (SGOT) and ALT(SGPT) Less than or equal to 3 X ULN

EXCLUSION CRITERIA:

The subject must be excluded from participating in the trial if the subject:

* Has a diagnosis of acute promyelocytic leukemia (APL)
* Has previously received an allogeneic hematopoietic stem cell transplant.
* Has received AML treatment with an investigational therapy or device within 4 weeks of the first dose of treatment.
* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
* Has a known history of active TB (Bacillus Tuberculosis)
* Has hypersensitivity to pembrolizumab or any of its excipients.
* Has hypersensitivity to decitabine or any of its excipients.
* Has received more than two prior cycles of decitabine.
* Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1.
* Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1.

  --Note: Subjects who have received cytoreductive therapy with hydroxyurea at any time prior to study Day 1 are an exception to this criterion.
* Has not recovered (i.e., less than or equal to Grade 1 or at baseline) from adverse events due to previously administered AML therapy agents.

  * Note: Subjects with less than or equal to Grade 2 neuropathy are an exception and may qualify for the study.
  * Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
* Has a known additional malignancy that is progressing or requires active treatment. Patients with basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer would not be excluded.
* Has known malignant central nervous system (CNS) involvement.
* Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
* Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis.
* Has an active infection requiring intravenous systemic therapy.
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
* Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
* Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
* Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist ) are live attenuated vaccines, and are not allowed.