Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
Inclusion Criteria:
- Pathologically confirmed myelodysplastic syndrome (MDS) diagnosis (regardless of
initial International Prognostic Scoring System [IPSS] risk category) or
oligoblastic acute myeloid leukemia (AML) with 21-30% bone marrow (BM) blasts in
whom DNMTi have failed; patients who have developed AML after DNMTi therapy can be
enrolled as long as they have initiated DNMTi therapy while they were in the MDS or
oligoblastic AML (20-30% BM blasts) phase and the study chair agrees; failure of
DNMTis is defined as: failure to achieve a complete response (CR), partial response
(PR) or hematologic improvement (HI) after at least 4 cycles of DNMTi or progressed
after such therapy
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Calculated creatinine clearance by Modification of Diet in Renal Disease (MDRD)
(CrCl) >= 60 ml/min/1.73 squared meter
- Total bilirubin =< 2.0 mg/dL unless due to Gilbert's syndrome, hemolysis, or
ineffective hematopoiesis
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])
and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =<
3 x upper limit of normal (ULN)
- Females of childbearing potential must have a negative serum or urine pregnancy test
within 72 hours prior to start of first cycle of therapy
- Patients must have no clinical evidence of central nervous system (CNS) or pulmonary
leukostasis, disseminated intravascular coagulation, or CNS leukemia
- Patients must have no serious or uncontrolled medical conditions
- The effects of entinostat and MK-3475 (pembrolizumab) on the developing human fetus
are unknown; for this reason, women of child-bearing potential and men who are
sexually active with women of childbearing potential must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry and for the duration of study participation; should a woman become
pregnant or suspect she is pregnant while she or her partner is participating in
this study, she should inform her treating physician immediately; men who are
sexually active with women of childbearing potential, treated or enrolled on this
protocol must also agree to use adequate contraception prior to the study, for the
duration of study participation, and 4 months after completion of entinostat and
MK3475 (pembrolizumab) administration
- Ability to understand and the willingness to sign a written informed consent
document
- Patients, who relapsed 6 months after bone marrow transplant and have no evidence of
active graft versus host disease and are off systemic immunosuppressant medications
for at least 2 months and have received hypomethylating agents (HMA) therapy before
or after transplant and meet other eligibility criteria of progression after at
least 4 months of DNMTi therapy, are eligible to be enrolled in this clinical trial
- Patients who are human immunodeficiency virus (HIV) positive may participate IF they
meet the following eligibility requirements:
- Must be on an effective anti-retroviral therapy with undetectable viral load
within 6 months are eligible for this trial
- They must have a CD4 count of greater than 250 cells/mcL
- They must not be receiving prophylactic therapy for an opportunistic infection
Exclusion Criteria:
- Any patients eligible for allogeneic stem cell transplantation (allo-SCT) and
willing to undergo allo-SCT as determined at time of screening for trial; patients
who are ineligible or not interested in undergoing allo-SCT will be eligible for the
trial
- Any serious medical condition, uncontrolled intercurrent illness (e.g., active
infection, symptomatic congestive heart failure [CHF], unstable angina, cardiac
arrhythmias, laboratory abnormalities, or psychiatric illness and/or biopsychosocial
conditions that may limit compliance
- Patients with known active cancers who are on therapy for those cancers at time of
screening
- Patients with a known positive test for hepatitis B virus surface antigen (HBV sAg)
or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic
infection might be enrolled if the viral load by polymerase chain reaction (PCR) is
undetectable with/without active treatment
- Pregnant or breast feeding females (lactating females must agree not to breast feed
while taking the study drugs)
- Use of any other experimental drug or therapy within 21 days of baseline - patients
who have had chemotherapy or radiotherapy within 4 weeks of entering the study or
those who have not recovered from adverse events due to agents administered more
than 4 weeks earlier
- Known hypersensitivity to MK-3475 (pembrolizumab) or history of allergic reactions
to compounds of similar chemical or biologic composition to anti-PD1 or PD-L1
antibodies or entinostat
- Prior treatment with any anti-PD-1 blocking therapies or histone deacetylase
inhibitors (HDACi), or anti-CTLA-4 antibody, CD137 agonist or other immune
activating therapy such as anti-CD 40 antibody within the last 3 months of
enrollment in the study
- Any history of active or severe autoimmune disease: inflammatory bowel disease,
including ulcerative colitis and Crohn's disease, rheumatoid arthritis, systemic
progressive scleroderma, systemic lupus erythematosus, autoimmune vasculitis (e.g.,
Wegener's granulomatosis), CNS or motor neuropathy considered of autoimmune origin
(e.g. Guillain-Barre syndrome, myasthenia gravis, multiple sclerosis); patients with
hypothyroidism with stable hormone replacement therapy dosing are allowed on study
- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis