Pomalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin for Relapsed/Refractory Multiple Myeloma

This is a phase 1/2, multicenter, open label and nonrandomized study to evaluate the efficacy and safety of pomalidomide at daily dosages of 2, 3 or 4 mg in combination with intravenous (IV) dexamethasone at 40 mg/dose and Pegylated Liposomal Doxorubicin (PLD) at 5 mg/m2/dose for subjects with relapsed/refractory multiple myeloma (MM). The study consists of a screening period, followed by up to eight 28 day open label treatment cycles, a final assessment to occur 28 days after the end of the last treatment, and a follow-up period. Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28 day treatment cycles. Subjects are to be treated to a maximum response plus 2 additional cycles (no more than 8 cycles will be allowed) or complete 8 cycles of therapy without disease progression. Pomalidomide, dexamethasone and PLD will be administered on the appropriate cycle days as shown below. Cohort 1 Pomalidomide\* - 2 mg, Dexamethasone\*\* - 40 mg, PLD\*\* - 5 mg/m2 Cohort 2 Pomalidomide\* - 3 mg, Dexamethasone\*\* - 40 mg, PLD\*\* - 5 mg/m2 Cohort 3 Pomalidomide\* - 4 mg, Dexamethasone\*\* - 40 mg, PLD\*\* - 5 mg/m2 \* PO Days 1-21 \*\* IV Days 1, 4, 8 and 11 In all cohorts, if an unacceptable dose limiting toxicities (DLT) is not seen in any of the 3 subjects during the first cycle of any dose level, dose escalation will continue. All subjects in a cohort must complete a minimum of 28 days or a full cycle, whichever is longer, without a DLT before enrollment to the next cohort can begin. If a DLT is identified in 1 subject at any dose level during the first treatment cycle, an additional 3 subjects will be recruited to this dose level. A maximum of 6 subjects may be enrolled in each cohort. If an unacceptable DLT is observed in 2 subjects at any dose level, no further subjects will be recruited to this dose level. The maximum tolerated dose (MTD) will be declared as the highest dose level at which fewer than 33% of subjects experienced an unacceptable DLT. If pomalidomide at 4 mg is reached and fewer than 33% of subjects experience an unacceptable DLT, 4 mg will be accepted as the putative MTD. Once the MTD is established, further enrollment will continue to expand that dose cohort until the total sample size of 40 subjects is reached for the entire study. During the phase 2 portion of this study, subjects enrolled will have relapsed/refractory MM resistant to lenalidomide as demonstrated by progressive disease while on lenalidomide or that has relapsed within 8 weeks of the last dose of lenalidomide.