Carfilzomib Thalidomide and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma
Status:
Recruiting
Trial end date:
2022-06-01
Target enrollment:
Participant gender:
Summary
All patients with multiple myeloma (MM) are destined to relapse even with the best available
approved agents. Median OS from diagnosis in the current era is reported at 5.4 years. Given
that myeloma remains an incurable disease, future improved OS is therefore reliant on the
expansion of salvage options for patients with RRMM.
Carfilzomib (formerly PR-171) is a tetrapeptide epoxyketone-based irreversible inhibitor of
the 20S proteasome. This second-generation proteasome inhibitor (PI) is structurally and
mechanistically different to the dipeptide boronic acid PI, bortezomib. Compared to
bortezomib, carfilzomib showed less off-target activity that may account for the reduced
myelosuppression and reduced neuropathy that is observed compared to bortezomib. As
monotherapy, carfilzomib has demonstrated robust and durable activity in heavily pre-treated
patients with RRMM in phase I and II trials The idea of combining a PI and an
immunomodulatory drug (IMiD) such as thalidomide or lenalidomide is attractive in MM due to
the efficacy previously demonstrated with combination bortezomib, thalidomide and
dexamethasone. Such efficacy obviates the need for chemotherapy that is known to induce
genetic instability and in turn gives rise to secondary cancers. In combination with
lenalidomide (25mg), Niesvizky and colleagues have demonstrated a maximum planned dose (MPD)
of carfilzomib as 20/27 mg/m2 with promising safety and efficacy. Combination carfilzomib and
thalidomide, as opposed to lenalidomide, is practically a more affordable regimen that will
be more applicable to the Asia-Pacific region.
Phase:
Phase 2
Details
Lead Sponsor:
National University Hospital, Singapore
Collaborators:
Celgene International Myeloma Foundation International Myeloma Foundation (IMF) The Australasian Leukaemia & Lymphoma Group (ALLG)