Phase 1b Study of Pembrolizumab, Decitabine +/- Venetoclax Combination Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
This phase Ib trial studies the side effects and best dose of pembrolizumab and how well it works in combination with decitabine with or without venetoclax in treating patients with acute myeloid leukemia or myelodysplastic syndrome that is newly-diagnosed, has come back (recurrent), or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. This trial may help doctors find the best dose of pembrolizumab that can be safely given in combination with decitabine with or without venetoclax, and to determine what side effects are seen with this treatment.
• Documented informed consent of the participant and/or legally authorized representative
• Agreement to allow the use of archival blood samples and marrow from diagnostic tumor biopsies. If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Eastern Cooperative Oncology Group (ECOG) status =\< 1
• Histologically confirmed AML (not including acute promyelocytic leukemia) or MDS
• Patients with the following diagnoses
‣ Refractory/relapsed AML by World Health Organization (WHO) classification, who are not candidates for allogeneic stem cell transplantation or potentially curative chemotherapy (Extramedullary disease is allowed).
⁃ MDS by WHO Classification who have failed to respond or relapsed after previous therapies
• Must have a life expectancy of \>= 3 months
• Fully recovered (=\< grade 1) from the acute toxic effects (except alopecia) or complications of prior anti-cancer therapy, including surgery
• Cannot be a candidate for allogeneic hematopoietic cell transplantation (alloHCT) within 90 days of starting treatment on the protocol and should be off pembrolizumab for at least 30 days to become eligible for alloHCT post-protocol therapy
• White blood cells (WBC) =\< 25 x 10\^9/L prior to initiation of venetoclax. Cytoreduction with hydroxyurea prior to treatment and/or during cycles 1 and/or 2 may be required
• Total bilirubin =\< 2 x upper limit of normal (ULN) (unless has Gilbert's disease)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN
• Creatinine clearance of \> 30 mL/min per 24-hour urine test or the Cockcroft-Gault formula
• International normalized ratio (INR) OR prothrombin time (PT) =\< 1.5 x ULN
• Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN
• Left ventricular ejection fraction (LVEF) \>= 50%
• Pulmonary function tests diffusion capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) \> 50% predicted
• Corrected QT (QTc) =\< 480 ms, Note: electrocardiogram (ECG) (single-read) to be performed within 14 days prior to day 1 of protocol therapy
• Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), and active hepatitis B virus (HBV) (surface antigen negative)
‣ If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed
• Meets other institutional and federal requirements for infectious disease titer requirements
‣ Note: Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
• Agreement by males and females of childbearing potential to use an effective birth control method of low user dependency or abstain from heterosexual activity from 4 weeks prior to first dose of treatment throughout the study treatment period and 3 (males) to 4 (females) months from the last dose of treatment
‣ Childbearing potential is defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
• Also, male subjects should refrain from sperm donation from the start of treatment throughout the study treatment period and for 6 months following the last dose of treatment