Salsalate, Venetoclax, and Decitabine or Azacitidine for the Treatment of Acute Myeloid Leukemia or Advanced Myelodysplasia/Myeloproliferative Disease
Condition: Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myeloblasts 10 Percent or More of Bone Marrow Nucleated Cells; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Myelodysplastic Syndromes; Myeloproliferative Disorders
Intervention: Azacitidine; Decitabine; Salsalate; Venetoclax
Intervention description: Given IV; Given IV; Given PO; Given PO
Intervention MeSH terms: Salicylsalicylic acid; Sodium Salicylate; Azacitidine; Decitabine; Venetoclax
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects of salsalate when added to venetoclax and
      decitabine or azacitidine in treating patients with acute myeloid leukemia or
      myelodysplasia/myeloproliferative disease that has spread to other places in the body
      (advanced). Drugs used in chemotherapy, such as salsalate, venetoclax, decitabine, and
      azacitidine work in different ways to stop the growth of cancer cells, either by killing the
      cells, by stopping them from dividing, or by stopping them from spreading.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically proven acute myelogenous leukemia (AML) or advanced myeloid malignancy
             [myelodysplasia; chronic myelomonocytic leukemia (CMML); or chronic myeloproliferative
             disease (MPD) each with >= 10% myeloblasts in blood or bone marrow]

          -  For patients with de novo AML: must not be a candidate for standard induction therapy
             based upon age, co-morbidities, patient choice, high risk features known to have poor
             outcomes with standard induction therapy (ELN high risk disease by cytogenetics,
             deoxyribonucleic acid [DNA] mutation profile or TP53 mutation)

          -  Patients with advanced myelodysplastic syndrome (MDS), secondary AML,
             relapsed/refractory AML, prior hypomethylating agent are eligible

          -  Patients must give informed consent

          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =<
             2

          -  Total bilirubin < 2 x upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             < 2.5 X institutional ULN

          -  Creatinine < 2 mg/dL

        Exclusion Criteria:

          -  White blood cell (WBC) uncontrolled (> 15,000/uL) despite hydroxyurea or cytarabine x
             3 days. Known central nervous system (CNS) AML

          -  Serious concomitant systemic disorders (including active infections) that would
             compromise the safety of the patient or compromise the patient?s ability to complete
             the study, at the discretion of the investigator. Pregnant patients are excluded

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to Salsalate or other agents used in the study. Examples include aspirin

          -  The effects of venetoclax and decitabine or 5-azacytidine on the developing human
             fetus at the recommended therapeutic dose are unknown. For this reason and because
             therapeutic agents used in this trial are known to be teratogenic, women of
             child-bearing potential and men must agree to use adequate contraception (hormonal or
             barrier method of birth control; abstinence) prior to study entry, for the duration of
             study participation and for 24 weeks after. Should a woman become pregnant or suspect
             she is pregnant while participating in this study, she should inform her treating
             physician immediately

          -  Patients with immune deficiency are at increased risk of lethal infections when
             treated with marrow-suppressive therapy, therefore, known human immunodeficiency virus
             (HIV)-positive patients receiving combination anti-retroviral therapy are excluded
             from the study because of possible pharmacokinetic interactions with treatment
             medications or other agents administered during the study