Japanese Phase 2 Study to Evaluate the Efficacy and Safety of Pomalidomide in Subjects With Relapsed and Refractory Multiple Myeloma

A Phase 2, Multicenter, Single-arm, Open-label Study in Japan to Evaluate the Efficacy and Safety of Pomalidomide (CC-4047) in Combination With Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma

The purpose of this study is to evaluate the efficacy and safety of pomalidomide in combination with dexamethasone in subjects with relapsed and refractory multiple myeloma.

Inclusion Criteria:

• 1. Must be ≥ 20 years of age at the time of signing the informed consent document.

  2. The subject must understand and voluntarily sign an informed consent document before any study related assessments/procedures are conducted.

  3. Must be able to adhere to the study visit schedule and other protocol requirements.

  4. Have a documented diagnosis of multiple myeloma and have relapsed and refractory disease. Subjects must have received at least 2 prior therapies. Subjects must have relapsed after having achieved at least stable disease for at least one cycle of treatment to at least one prior regimen and then developed progressive disease(PD). Subjects must also have documented evidence of progressive disease(PD) during or within 60 days (measured from the end of the last cycle) of completing treatment with the last antimyeloma drug regimen used just prior to study entry (refractory disease).

  5. Subjects must have undergone prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of bortezomib (either in separate regimens or within the same regimen).

  6. Subjects must have documented diagnosis of multiple myeloma and have measurable disease (serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24 hours).

  7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.

  8.Must agree to comply to pomalidomide Pregnancy Prevention Risk Management Plan.

Exclusion Criteria:

• 1. Pregnant or breastfeeding females 2. Hypersensitivity to thalidomide, lenalidomide, or dexamethasone 3. ≥ Grade 3 rash during prior thalidomide or lenalidomide therapy 4. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment will not be eligible to participate in this study 5. Any of the following laboratory abnormalities:

  • Absolute neutrophil count < 1,000/µL
  • Platelet count < 75,000/µL for subjects in whom < 50% of bone marrow nucleated cells are plasma cells; or a platelet count < 30,000/µL for subjects in whom ≥ 50% of bone marrow nucleated cells are plasma cells
  • Creatinine Clearance < 45 mL/min according to Cockcroft-Gault formula

Cockcroft-Gault estimation of Creatinine Clearance:

• Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L)

• Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior Red blood cell transfusion or recombinant human erythropoietin use is permitted)

• Serum glutamic oxaloacetic transaminase(SGOT)/aspartate aminitransferase(AST) or serum glutamic pyruvic transaminase(SGPT)/alanine aminotransferase(ALT) > 3.0 x upper limit of normal(ULN)

• Serum total bilirubin > 2.0 mg/dL (34.2 μmol/L); or ≥ 3.0 x upper limit of normal (ULN) for subjects with hereditary benign hyperbilirubinemia.

  6. Subjects with any one of the following:

• Congestive heart failure (New York Heart Association Class III or IV)

• Myocardial infarction within 12 months prior to starting study treatment

• Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris 7. Peripheral neuropathy ≥ Grade 2. 8. Prior history of malignancies, other than multiple myeloma, unless the subject has been free of the disease for ≥ 5 years. Exceptions include the following:

• Basal or Squamous cell carcinoma of the skin

• Carcinoma in situ of the cervix or breast

• Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b) 9. Known infection with human immunodeficiency virus (HIV) antibody positive, hepatitis B virus surface antigen (HBsAg) positive or hepatitis C virus antibody (HCVAb) positive. If negative for hepatitis B virus surface antigen (HBsAg) but hepatitis B core antibody (HBcAb) and/or hepatitis B surface antibody (HBsAb) positive status, a hepatitis B virus DNA test will be performed and if positive the subject will be excluded.

  10. Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide.

  11. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.

  12. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.

  13. Any condition that confounds the ability to interpret data from the study. 14. Previous therapy with pomalidomide. 15. Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of treatment.

  16. Subjects with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis, and lupus, which likely need additional steroid or immunosuppressive treatments in addition to the study treatment. Includes subjects receiving corticosteroids (> 10 mg/day of prednisone or equivalent) within 3 weeks prior to enrollment.

  17. Subjects who received any of the following within the last 14 days of initiation of study treatment:

• Plasmapheresis

• Major surgery (kyphoplasty is not considered major surgery)

• Radiation therapy

• Use of any antimyeloma drug therapy. 18. Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant less than 12 months prior to initiation of study treatment and who have not discontinued immunosuppressive treatment for at least 4 weeks prior to initiation of study treatment and are currently dependent on such treatment.

  19. Subjects who are planning for or who are eligible for stem cell transplant.