High Dose Cytarabine Followed by Pembrolizumab in Relapsed/Refractory AML

Inclusion Criteria

• Willing and able to provide written informed consent for the trial
• > 18 years and 4 cycles of azacitidine/decitabine or the equivalent experimental therapy (the latter as confirmed by the PI)
• Cytoreduction allowed with hydroxyurea and/or leukapheresis for up to 14 days prior to D1 of treatment under LCCC1522. Patients must be off hydroxyurea for > 12 hours prior to D1 of treatment under LCCC1522
• Demonstrate adequate organ function as defined below. All screening labs should be performed within 14 days of D1 of treatment under LCCC1522.

Serum creatinine ≤1.5 X upper limit of normal (ULN) OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl)-- ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN Serum total bilirubin ≤ 1.5 X ULN unless due to Gilbert's Disease, hemolysis or leukemic infiltration OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN Aspartate Aminotransferase (AST)(SGOT) and Alanine Aminotransferase (ALT) (SGPT) ≤ 5 X ULN International Normalized Ratio (INR) or Prothrombin Time (PT)- ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants or patient has disseminated intravascular coagulation deemed by investigator to be due to leukemia Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants or patient has disseminated intravascular coagulation deemed by investigator to be due to leukemia

• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of HiDAC treatment and again prior to D1 of pembrolizumab treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential should be willing to use adequate method of contraception for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. The two birth control methods can be two barrier methods or a barrier method plus a hormonal method to prevent pregnancy. Subjects should start using birth control from the screening visit throughout the study period up to 120 days after the last dose of study therapy.

Note: Abstinence is acceptable if this is the usual lifestyle preferred contraception for the subject.

• Male subjects must agree to use an adequate method of contraception starting with D1 of HiDAC 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.

• As determined by the enrolling physician or protocol designee, ability of the patient to understand and comply with study procedures

Exclusion Criteria

• Is currently participating in or has participated in a study of an investigational agent or using an investigational 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 HiDAC treatment. Note: use of steroid eye drops starting at the time of HiDAC administration is allowed.
• Has a known history of active Bacillus Tuberculosis (TB)
• Hypersensitivity to pembrolizumab or any of its excipients
• Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or