A Phase 1/2 Study of Pomalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin for Patients With 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.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of Pomalidomide
Phase 1: To establish the MTD of pomalidomide in combination with dexamethasone and pegylated liposomal doxorubicin
12 months
Yes
James R Berenson, MD
Principal Investigator
Oncotherapeutics
United States: Food and Drug Administration
PO-MM-PI-0049
NCT01541332
February 2012
April 2014
Name | Location |
---|---|
James R Berenson, MD, Inc. | West Hollywood, California 90069 |