This trial will evaluate the efficacy and safety of combination 3rd line treatment of Pomalidomide (POM) and low-dose Dexamethosone (LD-Dex) in subjects with relapsed or refractory multiple myeloma who have received a second line treatment of lenalidomide plus dexamethasone.

This trial will test the hypothesis that the proportion of patients will have an Overall Response Rate (ORR) of > 30 % to reveal that Pomalidomide is efficacious in pre-treated patients who are refractory to lenalidomide.

This is a multi-center, single-arm, open-label, phase 2 trial designed to further evaluate the efficacy and safety of combination Pomalidomide and Low Dose-Dexamethasone in subjects with relapsed or refractory multiple myeloma who have become refractory to a second line treatment of lenalidomide.

This trial will assess, Overall Response Rate (ORR), Overall Survival (OS), Progression-Free Survival (PFS), Duration of Response (DoR), Time to Response (TTR), Time to Progression(TTP) and safety.

Inclusion Criteria:

• 1. Adults ( age ≥ 18 years at the time of signing the informed consent document) with documented diagnosis of multiple myeloma and measurable disease (serum M-protein ≥ 0.5 dL or urine M-protein ≥ 200 mg/24 hours).

  2. Subjects must have received 2 prior treatment lines of anti-myeloma therapy, the most recent being lenalidomide plus dexamethasone. One prior line of therapy may consist of all predetermined components of induction followed by autologous stem cell transplantation and maintenance. A new treatment line is defined as one that was started after documented progressive disease.

  3. All subjects must have received at least 2 consecutive cycles of lenalidomide plus dexamethasone as the second line treatment regimen.

  4. Subjects must have either relapsed or refractory disease defined as documented disease progression during or within 60 days of completing their second-line myeloma therapy

  • Relapsed. Subjects who have relapsed after having achieved stable disease or better for at least 2 cycles of treatment during the second line treatment regimen and then developed progressive disease.
  • Refractory. Subjects who have developed progressive disease during the second-line treatment regimen after having received at least 2 cycles of treatment or within 60 days of completing the regimen.

    5. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.

    6. Subjects must understand and voluntarily sign an informed consent prior to any study related assessments/procedures being conducted.

    7. All subjects must provide an adequate bone marrow sample at screening that definitively evaluates the presence or absence of myelodysplastic changes.

    8. Females with child-bearing potential (FCBP† ) must agree to use 2 reliable forms of contraception simultaneously or practice complete abstinence from heterosexual contact for at least 28 days before starting study drug, while participating in the study (including during dose interruptions), and for at least 28 days after study treatment discontinuation and must agree to regular pregnancy testing during this timeframe.

    9. Females must agree to abstain from breastfeeding during study participation and 28 days after study drug discontinuation.

    10. Males must agree to use a latex condom during any sexual contact with female of childbearing potential (FCBP) while participating in the study and for 28 days following discontinuation from this study, even if he has undergone a successful vasectomy.

    11. Males must also agree to refrain from donating semen or sperm during the treatment phase and for 28 days after discontinuation from this study treatment.

    12. All subjects must agree to refrain from donating blood while on study therapy and for 28 days after discontinuation from this study treatment.

Exclusion Criteria:

• 1. 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.
  • Severe renal impairment (Creatinine Clearance < 30 mL/min) requiring dialysis.
  • Corrected serum calcium > 11.5 mdL (> 2.8 mmol/L)
  • Hemoglobin < 8 dL (< 4.9 mmol/L; prior red blood cell transfusion or recombinant human erythropoietin use is permitted)
  • Serum glutamic-oxaloacetic transaminase(SGOT)/ aspartate aminotransferase or glutamic-pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) > 3.0 x ULN
  • Serum total bilirubin > 2.0 mdL (34.2 μmol/L); or > 3.0 x ULN for subjects with hereditary benign hyperbilirubinemia 2. Prior history of malignancies, other than multiple myeloma, unless the subject has been free of the disease for ≥ 5 years. Allowed exceptions include the following:
  • Basal or squamous cell carcinoma of the skin
  • Carcinoma in situ of the cervix or breast
  • Incidental histological finding of prostate cancer (TNM [tumor, nodes, metastasis] stage of T1a or T1b) 3. Previous therapy with Pomalidomide 4. Hypersensitivity to thalidomide, lenalidomide, or dexamethasone (this includes ≥ Grade 3 rash during prior thalidomide or lenalidomide therapy) 5. 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.

    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's variant angina pectoris 7. Subjects who received any of the following within 14 days of initiation of study treatment:
  • Major surgery (kyphoplasty is not considered major surgery)
  • Use of any anti-myeloma drug therapy 8. Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of treatment, unless approved by the sponsor.

    9. Incidence of gastrointestinal disease that may significantly alter the absorption of Pomalidomide.

    10. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment 11. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent document.

    12. Pregnant or breastfeeding females 13. Known Human immunodeficiency virus positivity; active infectious hepatitis A, B, or C; or chronic hepatitis B or C