Safety and Efficacy Study of CC-486 in Subjects With Myelodysplastic Syndromes

Inclusion Criteria

• Male or female, ≥ 18 years of age at the time of signing the informed consent document
• Documented diagnosis of MYELODYSPLASTIC SYNDROMES (MDS), classified according to FRENCH-AMERICAN BRITISH (FAB) classification criteria
• Adequate course of treatment with an injectable hypomethylating agent (azacitidine for injection or decitabine) as the last therapeutic intervention for MDS prior to beginning screening for this study. Adequate is defined as:
• having received at least 6 consecutive 4-week treatment cycles with azacitidine for injection, or
• having received at least 4 consecutive 6-week treatment cycles with decitabine (3-day regimen) or at least 6 consecutive 4-week treatment cycles with decitabine (5-day regimen), or
• having demonstrated inability to tolerate treatment with an injectable hypomethylating agent because of unacceptable drug-related toxicity after at least 3 months of attempted treatment: Three 28-day cycles of azacitidine for injection or decitabine 5-day regimen; two 42-day cycles of decitabine 3-day regimen.
• Documented disease progression or stable disease as best response to treatment (or attempted treatment) with azacitidine for injection or decitabine. Those achieving an objective response to treatment regimen with an injectable hypomethylating agent (HMA) are excluded from participation in this study.

Definitions of disease progression are modified from INTERNATIONAL WORKING GROUP (IWG) 2006 criteria and include:

• Pre-injectable hypomethylating agent baseline bone marrow myeloblasts:
• Less than 5%: ≥ 100% increase to ≥ 8% blasts
• ≥ 5%: ≥ 50% increase to ≥ 10% blasts Note: ≥ 30% blasts is considered acute myeloid leukemia (AML )per FAB classification. Subjects known to have ≥ 30% blasts are not eligible for inclusion in this study.recognizing eastern cooperative oncology group) limitations of blast cell quantification, Protocol will allow subjects with pre-enrollment bone marrow blast counts up to 33% on the screening bone marrow examination to be considered for inclusion. Assessment may be made according to local bone marrow examination to facilitate enrollment of eligible subjects into the treatment phase of the study.
• Any clinical worsening from pre-injectable hypomethylating agents (HMA) baseline condition, including:
• sustained clinically-significant worsening (investigator's assessment) from baseline granulocyte, platelet, or hemoglobin values (≥ 2 values, separated by ≥ 2 weeks) - worsening granulocytes should be ≥ 50% decrease from pre-injectable HMA baseline value - worsening platelets should be ≥ 50% decrease from pre-injectable HMA baseline value (untransfused)
• worsening hemoglobin should be ≥ 1.5 g/dL decrease from preinjectable HMA baseline value in subjects not receiving RBC transfusions
• meaningful worsening in RBC or platelet transfusion requirement

Definition of stable disease is based on modified IWG 2006 criteria:

• Failure to achieve any objective response (CR - complete remission, PR - partial remissino, mCR - marrow complete remission, or HI - hematologic improvement), but no evidence of disease progression within the 8 weeks leading to the subject's first dose of investigational product (IP), Cycle 1, Day 1
• Have the last dose of the prior treatment regimen injectable HMA - (azacitidine for injection or decitabine) not more than 16 weeks prior to screening for this study (date of informed consent signature).
• No less than 3 weeks between the last dose of the prior treatment regimen injectable HMA - (azacitidine for injection or decitabine) and the planned date of first dose of IP (
• Have an eastern cooperative oncology group (ECOG) performance status of 0, 1, or 2
• Females subjects of childbearing potential (FCBP)1 may participate, providing they meet the following conditions:
• Have two negative pregnancy tests as verified by the investigator prior to starting any IP therapy: serum pregnancy test at screening and ne