Clinical trial NCT01519011 (phase 1, status: completed)
Conditions: myelodysplastic syndromes, leukemia, myelomonocytic, chronic, leukemia, myeloid, acute
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: oral azacitidine, oral azacitidine
SMILES: NC1=NC(=O)N(C=N1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O, NC1=NC(=O)N(C=N1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Eligibility criteria:

        Inclusion Criteria:

          -  Age 18 years or older at the time of signing the informed consent document

          -  Diagnosis of Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia and Acute
             Myeloid Leukemia

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

          -  At least 3 month life expectancy

          -  Adequate organ function, defined as:

               -  Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN);

               -  Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5
                  times the ULN;

               -  Serum creatinine ≤ 1.5 times the ULN;

               -  Serum bicarbonate ≥ 20 mEq/L

          -  Females of childbearing potential (FCBP) must:

               -  Agree to use at least two effective contraceptive methods (oral, injectable, or
                  implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier
                  contraceptive with spermicide; or vasectomized partner) throughout the study, and
                  for 3 months following the last dose of oral azacitidine; and

               -  Have a negative serum or urine pregnancy test (investigator's discretion;
                  sensitivity of at least 25 mIU/mL) at screening; and

               -  Have a negative serum or urine pregnancy test (investigator's discretion;
                  sensitivity of at least 25 mIU/mL) within 72 hours prior to Day 1 of the
                  pharmacokinetic (PK) phase (note that the screening pregnancy test can be used as
                  the test prior to Day 1 of the PK phase if it is performed within the 72 hour
                  timeframe).

          -  Males with partners who are FCBP must agree that they and their partners will use at
             least two effective contraceptive methods throughout the study and will avoid
             fathering a child for 3 months following the date of last oral azacitidine dosing

          -  Understand and voluntarily sign an informed consent document prior to the start of any
             study related assessments/procedures

          -  Able to adhere to the study visit schedule and other protocol requirements

        Exclusion Criteria:

          -  Suspected or proven acute promyelocytic leukemia based on morphology, immunophenotype,
             molecular assay, or karyotype

          -  Previous treatment with azacitidine or other demethylating agents within 21 days prior
             to starting study therapy or ongoing adverse events from previous treatment,
             regardless of the time period

          -  Anticancer therapy (standard or investigational) within 21 days prior to starting
             study therapy or ongoing adverse events from previous treatment, regardless of the
             time period

          -  Use of any proton pump inhibitor or any other agent that may affect gastric acid level
             within 28 days prior to study therapy (only applicable to Part II of the PK phase)

          -  Concurrent use of erythropoiesis-stimulating agents (ESAs) and other red blood cell
             hematopoietic growth factors, except that the subject is on a stable dose for at least
             4 weeks (28 days) prior to starting study therapy

          -  Concurrent use of iron-chelating agents, except that the subject is on a stable dose
             for at least 8 weeks (56 days) prior to starting study therapy

          -  Concurrent corticosteroid use, except for medical conditions other than
             Myelodysplastic Syndrome and provided the subject is on a stable or decreasing dose
             for ≥ 1 week prior to start study therapy

          -  Pregnant or lactating females

          -  Any known or suspected hypersensitivity to azacitidine or mannitol or any other
             ingredient used in the manufacture of oral azacitidine (see the azacitidine IB)

          -  Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing
             signs/symptoms related to the infection without improvement despite appropriate
             antibiotics or other treatment)

          -  Active viral infection with known human immunodeficiency virus (HIV) or viral
             hepatitis type B or C

          -  Presence of gastrointestinal disease, malignant hepatic tumors, or other conditions
             known to interfere with the absorption, distribution, metabolism, or excretion of
             drugs

          -  Current congestive heart failure (New York Heart Association Class III-IV Appendix G),
             unstable angina or angina requiring surgical or medical intervention within 6 months
             prior to starting study therapy, myocardial infarct within 6 months prior to starting
             study therapy, or uncontrolled cardiac arrhythmia (defined as arrhythmia that is
             symptomatic or requires treatment or asymptomatic sustained ventricular tachycardia).
             Subjects with controlled atrial fibrillation that is asymptomatic are eligible

          -  Any significant medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from participating in the study

          -  Any condition, including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study

          -  Any condition that confounds the ability to interpret data from the study