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

A Phase 2, Open-Label, Single-Arm Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneous Azacitidine in Adult Chinese Subjects With Higher-Risk Myelodysplastic Syndromes

The purpose of the study is to determine whether azacitidine is safe and effective in the treatment of Chinese patients with higher risk Myelodysplastic Syndromes (MDS).

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 Myelodysplastic Syndrome (MDS) and with an International Prognostic Scoring System (IPSS) score of intermediate-2 or high risk or a diagnosis of myelodysplastic chronic myelomonocytic leukemia (CMML) per modified FAB criteria meeting the following:

  • Monocytosis in peripheral blood > 1 x 10^9/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 10^9/L

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

• 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 Investigational Product (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.