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
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: pomalidomide; Dexamethasone
Intervention description: 4 mg pomalidomide capsules administered orally; 40 mg dexamethasone (or 20 mg for participants > 75 years of age) tablets administered orally
Intervention MeSH terms: Dexamethasone; Pomalidomide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 455.0
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

Summary:

      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