Study to Evaluate the Safety and Efficacy of Pomalidomide Monotherapy in Subjects With Refractory or Relapsed Refractory Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: pomalidomide
Intervention description: Oral pomalidomide 4 mg on Days 1-21 of 28-day cycle until progressive disease (PD) or unacceptable toxicity
Intervention MeSH terms: Pomalidomide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Myeloma; Multiple Myeloma; Relapsed Multiple Myeloma; Relapsed and Refractory Multiple Myeloma; Refractory Myeloma; Resistant Multiple Myeloma; Treatment-resistant Multiple Myeloma; Pomalidomide; Lenalidomide-resistant; Bortezomib-resistant; Companion

Summary:

      The purpose of this study is to evaluate the efficacy and safety of pomalidomide monotherapy
      in subjects with refractory or relapsed and refractory multiple myeloma who were enrolled in
      study CC-4047-MM-003 (NCT01311687) and discontinued treatment with high-dose dexamethasone
      due to disease progression.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects with refractory or relapsed and refractory multiple myeloma who were enrolled
             in Study CC-4047-MM-003 and discontinued study therapy with dexamethasone alone
             (Treatment Arm B) after at least starting the second cycle of dexamethasone treatment
             and due to development of documented disease progression according to the
             International Myeloma Working Group (IMWG) criteria and as decided by an Independent
             Review Adjudication Committee (IRAC).

          2. Must be ≥ 18 years at the time of signing the informed consent form.

          3. The subject must understand and voluntarily sign an informed consent document prior to
             any study related assessments/procedures being conducted. The only exception is if a
             skeletal survey was performed within 90 days prior to the start of Cycle 1, then a new
             survey will not be required.

          4. Must be able to adhere to the study visit schedule and other protocol requirements.

          5. Subjects must have documented diagnosis of multiple myeloma and have measurable
             disease (serum M-protein ≥ 0.5g/dL or urine M-protein ≥ 200 mg/24 hours).

          6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.

          7. Females of childbearing potential (FCBP†) must agree to utilize two reliable forms of
             contraception simultaneously or practice true abstinence [when this is in line with
             the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar,
             ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable
             methods of contraception]from heterosexual contact for at least 28 days before
             starting study drug, while participating in the study (including dose interruptions),
             and for at least 28 days after study treatment discontinuation and must agree to
             regular pregnancy testing during this timeframe.

          8. Females must agree to abstain from breastfeeding during study participation and 28
             days after study discontinuation.

          9. Males must agree to either use a latex condom during any sexual contact with FCBP or
             practice true abstinence [when this is in line with the preferred and usual lifestyle
             of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal,
             post-ovulation methods) and withdrawal are not acceptable methods of contraception]
             while participating in the study and for 28 days following discontinuation from this
             study, even if he has undergone a successful vasectomy. .

         10. Males must also agree to refrain from donating semen or sperm while on pomalidomide
             and for 28 days after discontinuation from this study treatment.

         11. All subjects must agree to refrain from donating blood while on study drug and for 28
             days after discontinuation from this study treatment.

         12. All subjects must agree not to share study medication

        Exclusion Criteria

          -  The presence of any of the following will exclude a subject from enrollment:

               1. Subjects with multiple myeloma who were not treated as a part of Study
                  CC-4047-MM-003 (Arm B).

               2. Subjects who received any anti-myeloma or anti-cancer therapies within the last
                  14 days of wash-out period before initiation of study treatment.

               3. Subjects who discontinued CC-4047-MM-003 study ≥120 days.

               4. Subjects who initiate another anti-myeloma therapy from the time of disease
                  progression on study CC-4047-MM-003 to the time of treatment initiation in the
                  companion study.

               5. Any of the following laboratory abnormalities:

                    -  Absolute neutrophil count (ANC) < 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 (If
                       creatinine clearance calculated from the 24-hour urine sample is ≥45 ml/min,
                       patient will qualify for the trial)

                    -  Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L);

                    -  Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior RBC transfusion or recombinant
                       human erythropoietin use is permitted)

                    -  Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN)

                    -  Serum total bilirubin > 2.0 mg/dL (34.2 μmol/L); or > 3.0 x ULN for subjects
                       with hereditary benign hyperbilirubinaemia

               6. Prior history of malignancies, other than Multiple Myeloma (MM), 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)

               7. Hypersensitivity to thalidomide or lenalidomide. (This includes ≥ Grade 3 rash
                  during prior thalidomide or lenalidomide therapy).

               8. Peripheral neuropathy ≥ Grade 2.

               9. 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.

              10. Subjects who are planning for or who are eligible for stem cell transplant.

              11. Subjects with any one of the following:

                    -  Congestive heart failure (NY 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

              12. 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

              13. Use of any investigational agents within 28 days or 5 half lives (whichever is
                  longer) of treatment.

              14. Subjects with chronic conditions such as rheumatoid arthritis, multiple sclerosis
                  and lupus, which likely need additional steroid or immunosuppressive treatments
                  in addition to the study treatment.

              15. Any condition including the presence of laboratory abnormalities, which places
                  the subject at unacceptable risk if he/she were to participate in the study.

              16. Incidence of gastrointestinal disease that may significantly alter the absorption
                  of pomalidomide.

              17. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment.

              18. Any serious medical condition, laboratory abnormality, or psychiatric illness
                  that would prevent the subject from signing the informed consent form.

              19. Pregnant or breastfeeding females.

              20. Known human immunodeficiency virus (HIV) positivity or active infectious
                  hepatitis A, B or C.