DEC-C and Thioguanine for R/R AML

Eligibility Criteria

• 1. Age ≥18 years of age
• 2. Patients must have histologically and cytologically confirmed R/R AML according to the World Health Organization classification based on documented bone marrow biopsy or peripheral blood specimens, with the exception of acute promyelocytic leukemia
• 1. Relapsed AML is defined as the detection of ≥5% blasts in the bone marrow or reappearance of leukemic blasts in the peripheral blood in a patient with prior remission
• 2. Refractory AML is defined as the failure to obtain a CR, CRh, or CRi after at least two courses of intensive induction (including hypomethylating agent plus venetoclax induction) or at least six cycles of a hypomethylating agent-based regimen (except venetoclax combinations as above)
• 3. Able to provide informed consent
• 4. Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2 or Karnofsky ≥60%
• 5. Adequate organ function defined by the following parameters:
• 1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5x the upper limit of normal (ULN)
• 2. Bilirubin ≤2x the ULN unless due to known Gilbert's disease or hemolysis due to blood transfusion
• 3. Calculated glomerular filtration rate (GFR) of ≥ 30 mL/min/1.73 m2
• 6. Prior hypomethylating agent is allowed
• 7. Female patients of childbearing potential must not be nursing or planning to become pregnant and require a negative urine or serum pregnancy test within 30 days of study therapy.
• 8. Female patients of childbearing potential must be willing to use at least 1 method of highly effective contraception during the study. 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.
• 9. Male patients treated or enrolled who are sexually active must agree to adequate contraception use and refrain from sperm donation throughout the duration of the study, and up to 4 months after completion of thioguanine and decitabine-cedazuridine.
• 10. Willing to provide pretreatment bone marrow aspirate and biopsies samples as well as subsequent bone marrow aspirate and biopsies samples during the study.
• 11. Ability to understand and the willingness to sign a written informed consent document.
• 1. Previously received thioguanine
• 2. Any anti-leukemic therapy, including investigational therapies, within 14 days of study treatment initiation. Hydroxyurea for blood count control is allowed throughout induction cycle(s)
• 3. Prior allogeneic hematopoietic stem cell transplantation within 3 months of study enrollment; active graft versus host disease
• 4. Clinical suspicion for active central nervous system (CNS) involvement by AML; previously treated CNS involvement is allowed
• 5. Second malignancy requiring treatment within 6 months of study enrollment, with the exception of non-melanoma skin cancers or cancers requiring hormonal therapy only
• 6. Active, uncontrolled infection
• 7. Human immunodeficiency virus (HIV) not controlled by standard therapy
• 8. Active hepatitis B or C infection. Participants whose infections are controlled with antiviral therapy are allowed.
• 9. Significant medical diseases or comorbidities, in the opinion of the investigator, that would preclude the safe participation in the study
• 10. Known hypersensitivity to DEC-C or thioguanine