Pembrolizumab and Decitabine for Refractory or Relapsed Acute Myeloid Leukemia

This is a pilot study to determine the feasibility of a novel combination of Pembrolizumab
and Decitabine in relapsed/refractory adult AML patients. While both Pembrolizumab and
Decitabine are FDA approved agents, this study will explore giving these drugs in combination
for this population of patients.

- 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.