Study of Azacitidine to Evaluate Safety and Effectiveness for Chinese Patients With Higher Risk Myelodysplastic Syndrome
Condition: Myelodysplastic Syndrome (MDS)
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: Azacitidine
Intervention description: Subcutaneous administration of azacitidine 75 mg/m^2/day for 7 days every 28 days optimally for at least 6 cycles until disease progression, unacceptable toxicity, or treatment discontinuation for any other reason
Intervention MeSH terms: Azacitidine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 72.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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).
    

Eligibility criteria:

        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.