Clinical trial NCT03306264 (phase 3, status: recruiting)
Conditions: myelodysplastic syndromes, chronic myelomonocytic leukemia, acute myeloid leukemia
ICD codes: D46.9, D46.C, D46.Z, C93.11, C93.12, C93.10, C92.A1, C92.A2, C92.61, C92.62, C92.A0, C92.60
Drugs: astx727, dacogen
SMILES: NC1=NC(=O)N(C=N1)[C@H]1C[C@H](O)[C@@H](CO)O1, NC1=NC(=O)N(C=N1)[C@H]1C[C@H](O)[C@@H](CO)O1
Eligibility criteria:

        Inclusion Criteria:

          1. Able to understand and comply with the study procedures, understand the risks involved
             in the study, and provide written informed consent before the first study-specific
             procedure; specifically able to comply with the PK assessment schedule during the
             first 2 treatment cycles.

          2. Men or women ≥18 years who are candidates to receive IV decitabine according to FDA or
             European Medicines Agency (EMA) approved indications:

               1. In North America: Participants with MDS previously treated or untreated with de
                  novo or secondary MDS, including all French-American-British subtypes (refractory
                  anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess
                  blasts, refractory anemia with excess blasts in transformation, and chronic
                  myelomonocytic leukemia [CMML]), and subjects with MDS International Prognostic
                  Scoring System (IPSS) int-1, -2, or high-risk MDS.

               2. In Europe: Participants with de novo or secondary AML, as defined by the World
                  Health Organization (WHO) criteria, who are not candidates for standard induction
                  chemotherapy.

          3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

          4. Adequate organ function defined as follows:

               1. Hepatic: Total or direct bilirubin ≤2 × upper limit of normal (ULN); aspartate
                  transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine
                  transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) ≤2.5 × ULN.

               2. Renal: serum creatinine ≤1.5 × ULN or calculated creatinine clearance or
                  glomerular filtration rate >50 mL/min/1.73 m2 for subjects with creatinine levels
                  above institutional normal.

          5. No major surgery within 30 days of first study treatment.

          6. Life expectancy of at least 3 months.

          7. Women of child-bearing potential must not be pregnant or breastfeeding and must have a
             negative pregnancy test at screening. Women of non-childbearing potential are those
             who have had a hysterectomy or bilateral oophorectomy, or who have completed
             menopause, defined as no menses for at least 1 year AND either age ≥65 years or
             follicle-stimulating hormone levels in the menopausal range.

          8. Subjects and their partners with reproductive potential must agree to use effective
             contraceptive measures during the study and for 3 months after the last dose of study
             treatment. Effective contraception includes methods such as oral contraceptives or
             double-barrier method (eg, use of a condom AND diaphragm, with spermicide).

        Exclusion Criteria:

          1. Prior treatment with more than 1 cycle of azacitidine or decitabine. Prior cytotoxic
             chemotherapy for AML except for hydroxyurea to control high white blood cell (WBC)
             counts.

          2. Hospitalization for more than 2 days for documented febrile neutropenia, pneumonia,
             sepsis, or systemic infection in the 30 days before screening.

          3. Treatment with any investigational drug or therapy within 2 weeks of study treatment,
             or 5 half-lives, whichever is longer, before the first dose of study treatment, or
             ongoing clinically significant adverse events (AEs) from previous treatment.

          4. Cytotoxic chemotherapy or prior azacitidine or decitabine within 4 weeks of first dose
             of study treatment.

          5. Concurrent MDS therapies, including lenalidomide, erythropoietin,
             cyclosporine/tacrolimus, granulocyte-colony stimulating factor (G-CSF),
             granulocyte-macrophage colony-stimulating factor, etc. (Prior treatment with these
             agents is permitted, provided that completion is at least 1 week before the first dose
             of study treatment.)

          6. Poor medical risk because of other conditions such as uncontrolled systemic diseases,
             active uncontrolled infections, or comorbidities that may put the patient at risk of
             not being able to complete at least 2 cycles of treatment.

          7. Known significant mental illness or other condition, such as active alcohol or other
             substance abuse or addiction, that in the opinion of the investigator predisposes the
             subject to high risk of noncompliance with the protocol.

          8. Rapidly progressive or highly proliferative disease (total white blood cell count of
             >15 × 10^9/L) or other criteria that render the subject at high risk of requiring
             intensive cytotoxic chemotherapy within the next 3 months.

          9. Life-threatening illness or severe organ system dysfunction, such as uncontrolled
             congestive heart failure or chronic obstructive pulmonary disease, or other reasons
             including laboratory abnormalities, which, in the investigator's opinion, could
             compromise the subject's safety, interfere with the absorption or metabolism of
             ASTX727, or compromise completion of the study or integrity of the study outcomes.

         10. Prior malignancy, except for adequately treated basal cell or squamous cell skin
             cancer, in situ cervical cancer, prostate cancer or breast cancer under control with
             hormone therapy, or other cancer from which the subject has been disease free for at
             least 2 years.