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
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.