Japanese Phase 2 Study to Evaluate the Efficacy and Safety of Pomalidomide in Subjects With Relapsed and Refractory Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Pomalidomide; Dexamethasone
Intervention description: 4 mg oral pomalidomide once daily Days 1-21 of each 28-day cycle; 40 mg or 20 mg oral dexamethasone once daily on Days 1, 8, 15, 22 of each 28-day cycle
Intervention MeSH terms: Dexamethasone; Pomalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Pomalidomide,; CC-4047,; Dexamethasone,; Relapsed and refractory multiple myeloma,; phase 2

Summary:

      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.
    

Eligibility criteria:

        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.