Combined Carfilzomib and Hydroxychloroquine in Patients With Relapsed/Refractory Multiple Myeloma
Status:
Active, not recruiting
Trial end date:
2022-01-01
Target enrollment:
Participant gender:
Summary
Multiple myeloma (MM) is a neoplastic expansion of bone marrow plasma cells. Despite advances
in treatment in recent years, MM is still a fatal disease. MM is characterized by the ability
of malignant cells to produce large amounts of monoclonal immunoglobulin. The secretion of
these immunoglobulins can be detected as the "M-protein" in serum, and the measurement of the
M-component is used both for diagnosis and to evaluate treatment response and relapse. The
high load of secreted proteins in MM cells requires a efficient way to clear these proteins
from the cells and targeting protein degradation is an important therapeutic target in MM.
This is today done by inhibiting the proteasome, one of the two central ways cells can
degrade proteins, by drugs named proteasome inhibitors (including bortezomib, ixazomib and
carfilzomib). Patients become resistant to these drugs, and it is therefore likely that
myeloma cells also utilise another important system for protein degradation, called
autophagy. Pre-clinical studies have shown that the combination of the proteasome inhibitor
carfilzomib and the autophagy inhibitor hydroxychloroquine increases myeloma cell death and
that hydroxychloroquine is able to reverse MM cell resistance to carfilzomib. This is the
rationale for this study, where the investigators add the autophagy inhibitor
hydroxychloroquine to a standard regime of carfilzomib and dexamethasone, to determine a
maximum tolerated dose of this combination and to study tolerability.