Study of Azacitidine to Evaluate Safety and Effectiveness for Chinese Patients With Higher Risk Myelodysplastic Syndrome

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

• Chinese males and females of Asian descent ≥ 18 years of age at the time of signing the informed consent document;

• Must have a documented diagnosis of refractory anemia with excess blasts (RAEB) or refractory anemia with excess blasts in transformation (RAEB-T) according to French-American-British (FAB) classification for MDS (Appendix A) and with an International Prognostic Scoring System (IPSS) score of intermediate-2 or high risk (Appendix D) or a diagnosis of myelodysplastic chronic myelomonocytic leukemia (CMML) per modified FAB criteria meeting the following:

  • Monocytosis in peripheral blood > 1 x 109/L;
  • Dysplasia in one or more myeloid cell lines;
  • 10% to 29% blasts in the bone marrow; and White blood cell (WBC) count < 13 x 109/L
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (see Appendix C);
• Adequate organ function, defined as:
• Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN);
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.0 times the ULN;
• Serum creatinine ≤ 1.5 times the ULN;
• Females of childbearing potential (FCBP) must:
• Agree to the use of a physician-approved contraceptive method (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on azacitidine; and
• for 3 months following the last dose of azacitidine; and have a negative serum pregnancy test within 72 hours prior to starting IP.
• Male subjects with a female partner of childbearing potential must agree to the use of a physician-approved contraceptive method throughout the course of the study and avoid fathering a child during the course of the study and for 3 months following the last dose of azacitidine;
• Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted;
• Able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

• Previous treatment with azacitidine or decitabine;
• Diagnosis of malignant disease within the previous 12 months (excluding basal cell carcinoma of the skin without complications, "in-situ" carcinoma of the cervix or breast,or other local malignancy excised or irradiated with a high probability of cure);
• Uncorrected red cell folate deficiency or vitamin B12 deficiency;
• Diagnosis of metastatic disease;
• Malignant hepatic tumors;
• Known or suspected hypersensitivity to azacitidine or mannitol;
• Candidate to proceed to bone marrow or stem cell transplant during the study;
• Prior transplantation or cytotoxic therapy, including azacitidine and chemotherapy,administered to treat MDS;
• Treatment with erythropoietin or myeloid growth factors (granulocyte colony-stimulating factor [G-CSF] or granulocyte-macrophage colony-stimulating factor [GM-CSF]) during the 21 days prior to Day 1 of Cycle 1;
• Treatment with androgenic hormones during the 14 days prior to Day 1 of Cycle 1;
• Active viral infection with known human immunodeficiency virus (HIV) or viral hepatitis type B or C;
• Treatment with other investigational drugs, including thalidomide and arsenic trioxide,within the previous 30 days prior to Day 1 of Cycle 1, or ongoing adverse events from previous treatment with investigational drugs, regardless of the time period; and
• Pregnant or lactating females;
• 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.