Efficacy and Safety Study of CC-5013 Monotherapy in Subjects With Myelodysplastic Syndromes

• ≥ 50% decrease in RBC transfusion requirement [ Designated as safety issue: No ]
• Platelet Response [ Designated as safety issue: No ]
  Platelet Response
• Neutrophil Response [ Designated as safety issue: No ]
  Neutrophil Response
• Bone marrow Response [ Designated as safety issue: No ]
  Bone marrow Response
• Duration of Response [ Designated as safety issue: No ]
  Duration of Response
• Hemoglobin concentration [ Designated as safety issue: No ]
  Change of hemoglobin concentration from baseline
• Number of Participants with Adverse Event [ Designated as safety issue: Yes ]
  Number of Participants with Adverse Event

This study is a multi-center, single-arm, open-label study of oral CC-5013 monotherapy administered at a dose of 10 mg daily on Days 1-21 every 28 days (28-day cycles) to red blood cell (RBC) transfusion-dependent subjects with low- or intermediate-1-risk MDS who do not have a del (5q31-33) cytogenetic abnormality. Screening procedures will take place within 28 days of first day of study drug treatment. Subjects will receive study drug (CC-5013) in 28-day cycles for up to 6 cycles, or until bone marrow disease progression or progression/relapse following erythroid hematologic improvement (Appendix I) is documented. Study visits will occur every cycle (every 28 days) and laboratory monitoring to assess hematological parameters will occur every 14 days. Safety and efficacy assessments to be performed during the study are outlined in the Schedule of Study Assessments.

Inclusion Criteria:

• Must understand and voluntarily sign an informed consent form.
• Age ≥ 18 years at the time of signing the informed consent form.
• Must be able to adhere to the study visit schedule and other protocol requirements.
• Diagnosis of low - or intermediate-1-risk IPSS (Appendix III) MDS without an abnormality of chromosome 5 involving a deletion between bands q31 and q33.
• Red blood cell (RBC) transfusion-dependent anemia defined as having received ≥ to 2 units of RBCs within 8 weeks of the first day of study drug treatment.
• Eastern Cooperative Oncology Group (ECOG) (Appendix IV) performance status score of 0, 1, or 2.
• Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test within 7 days of starting study drug.
• Sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on study drug.
• WCBP must agree to have pregnancy tests every 4 weeks while on study drug.

Exclusion Criteria:

• Pregnant or lactating females.
• Prior therapy with lenalidomide.
• An abnormality of chromosome 5 involving a deletion between bands q31 and q33.
• Lab Abnormality: Absolute neutrophil count (ANC) <500 cells/mm3 (0.5 x 109/L)
• Lab Abnormality: Platelet count <50,000/mm3 (50 x 109/L)
• Lab Abnormality: Serum creatinine >2.5 mg/dL (221 mmol/L)
• Lab Abnormality: Serum glutamic oxaloacetic transaminase/Aspartate transaminase (SGOT/AST) or Serum glutamic pyruvic transaminase/Alanine transaminase (SGPT/ALT) >3.0 x upper limit of normal (ULN)
• Lab Abnormality: Serum total bilirubin >2.0 mg/dL (34 mmol/L)
• Prior ≥ grade 3 National Cancer Institute (NCI) Common Toxicity Criteria (CTC) (Appendix VI) allergic reaction/hypersensitivity to thalidomide.
• Prior ≥ grade 3 NCI CTC (Appendix VI) rash or any desquamation (blistering) while taking thalidomide.
• Clinically significant anemia due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding
• If a marrow aspirate is not evaluable for storage iron, transferrin saturation must be > 20 % and serum ferritin not less than 50 ng/mL.
• Use of hematopoietic growth factors within 7 days of the first day of study drug treatment.
• Chronic use (>2 weeks) of greater than physiologic doses of a corticosteroid agent (dose equivalent to >10 mg/day of prednisone) within 28 days of the first day of study drug treatment.
• Use of experimental or standard drugs (i.e. chemotherapeutic, immunosuppressive, and cytoprotective agents) for the treatment of MDS within 28 days of the first day of study drug treatment.
• Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for greater than or equal to 3 years.
• Use of any other experimental therapy within 28 days of the first day of study drug treatment.