NCT04163107

Combined Carfilzomib and Hydroxychloroquine in Patients With Relapsed/Refractory Multiple Myeloma

Combined Carfilzomib and Hydroxychloroquine in Patients With Relapsed/Refractory Multiple Myeloma - a Phase 1 Trial

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 19 (actual)
• Sponsor: Norwegian University of Science and Technology · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Multiple Myeloma

Interventions

Type	Name	Description
DRUG	Hydroxychloroquine	All patients start with a 14 days run-in with monotherapy with hydroxychloroquine (HCQ) at their assigned dose level. Then they continue with 6 28-day cycles of HCQ/Carfilzomib/Dexamethasone. 3 patients at each dose level.
DRUG	Carfilzomib Injection	All patients start with a 14 days run-in with monotherapy with hydroxychloroquine (HCQ) at their assigned dose level. Then they continue with 6 28-day cycles of HCQ/Carfilzomib/Dexamethasone. 3 patients at each dose level.
DRUG	Dexamethasone	All patients start with a 14 days run-in with monotherapy with hydroxychloroquine (HCQ) at their assigned dose level. Then they continue with 6 28-day cycles of HCQ/Carfilzomib/Dexamethasone. 3 patients at each dose level.

Timeline

• Start date: 2020-01-07
• Primary completion: 2021-12-28
• Completion: 2021-12-28
• First posted: 2019-11-14
• Last updated: 2022-03-18

Locations

2 sites across 1 country: Norway