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

Conditions: Multiple Myeloma

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

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