A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-Dose Dexamethasone Versus High-Dose Dexamethasone in Subjects With Refractory Multiple Myeloma or Relapsed and Refractory Multiple Myeloma and Companion Study

The purpose of this study is to compare efficacy and safety of pomalidomide in combination with low-dose dexamethasone versus high-dose dexamethasone in subjects with refractory or relapsed and refractory multiple myeloma.


Eligibility Criteria:
Inclusion Criteria:

* Must be ≥ 18 years of age
* Subjects must have documented diagnosis of multiple myeloma and have measurable disease
* Subjects must have undergone prior treatment with ≥ 2 treatment lines of anti-myeloma therapy
* Subjects must have either refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last myeloma therapy
* All subjects must have received at least 2 consecutive cycles of prior treatment that included lenalidomide and bortezomib
* All subjects must have failed treatment with both lenalidomide and bortezomib in one of the following ways: 1) Documented progressive disease on or within 60 days of completing treatment with lenalidomide and/or bortezomib, or 2) In case of prior response \[≥ partial response (PR)\] to lenalidomide or bortezomib, subjects must have relapsed within 6 months after stopping treatment with lenalidomide and/or bortezomib-containing regimens, or 3) Subjects who have not had a ≥ minimal response (MR) and have developed intolerance/toxicity after a minimum of two cycles of lenalidomide- and/or bortezomib-containing regimen
* Patients must have received adequate prior alkylator therapy
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
* Females of childbearing potential (FCBP) must not become pregnant for 28 days prior to initiation of study drug, during the study, and for 28 days after discontinuation
* Females must agree to abstain from breastfeeding during study participation and 28 days after study drug discontinuation
* Males must agree to use a latex condom during any sexual during the study and for 28 days following discontinuation from this study
* Males must also agree to refrain from donating semen or sperm while on pomalidomide and for 28 days after discontinuation from this study

Exclusion Criteria:

* 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
  * Creatinine clearance \< 45 mL/min
  * Corrected serum calcium \> 14 mg/dL
  * Hemoglobin ≤ 8 g/dL
  * Serum glutamic oxaloacetic transaminase (SGOT)/ aspartate aminotransferase (AST) or transaminase, serum glutamic pyruvic (SGPT)/ alanine aminotransferase (ALT) \> 3.0 x upper limit of normal (ULN)
  * Serum total bilirubin \> 2.0 mg/dL
* Previous therapy with pomalidomide
* Hypersensitivity to thalidomide, lenalidomide, or dexamethasone
* Resistance to high-dose dexamethasone used in the last line of therapy
* Peripheral neuropathy ≥ Grade 2
* Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant
* Subjects who are planning for or who are eligible for stem cell transplant
* Subjects with any one of the following: 1) Congestive heart failure, 2) Myocardial infarction within 12 months prior to starting study treatment, 3) Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris
* Subjects who received any of the following within the last 14 days of initiation of study treatment: 1) Plasmapheresis, 2) Major surgery, 3) Radiation therapy, 4) Use of any anti-myeloma drug therapy
* Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of treatment
* Subjects with conditions requiring chronic steroid or immunosuppressive treatment
* Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
* Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide
* Subjects unable or unwilling to undergo antithrombotic prophylactic treatment
* Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subjects from signing the informed consent form
* Pregnant or breastfeeding females
* Known human immunodeficiency virus (HIV) positivity or active infectious hepatitis A, B, or C