NCT04163107: MYELOMA-HCQ

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

Completed Phase 1 Last updated 18 March 2022

What this trial tests

Phase 1 trial testing Hydroxychloroquine in Multiple Myeloma in 19 participants. Completed in 28 December 2021.

Timeline

7 January 2020

Primary endpoint
28 December 2021

28 December 2021

Quick facts

Lead sponsor	Norwegian University of Science and Technology
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	19
Start date	7 January 2020
Primary completion	28 December 2021
Estimated completion	28 December 2021
Sites	2 locations across Norway

Drugs / interventions tested

• Hydroxychloroquine (HYDROXYCHLOROQUINE) — full drug profile →
• Carfilzomib Injection — full drug profile →
• Dexamethasone (dexamethasone) — full drug profile →

Conditions studied

• Multiple Myeloma — all drugs for Multiple Myeloma →

Sponsor

Norwegian University of Science and Technology

Who can join

18 and older, any sex, with Multiple Myeloma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Autophagy and Autophagy-Related Diseases: A Review.
   Ichimiya T, Yamakawa T, Hirano T, Yokoyama Y, et al · · 2020 · cited 240× · PMID 33255983 · DOI 10.3390/ijms21238974
2. The Dual Role of Autophagy in Cancer Development and a Therapeutic Strategy for Cancer by Targeting Autophagy.
   Yun CW, Jeon J, Go G, Lee JH, et al · · 2020 · cited 147× · PMID 33375363 · DOI 10.3390/ijms22010179
3. Chloroquine against malaria, cancers and viral diseases.
   Zhou W, Wang H, Yang Y, Chen ZS, et al · · 2020 · cited 85× · PMID 32947043 · DOI 10.1016/j.drudis.2020.09.010
4. The Landscape of Signaling Pathways and Proteasome Inhibitors Combinations in Multiple Myeloma.
   Paradzik T, Bandini C, Mereu E, Labrador M, et al · · 2021 · cited 28× · PMID 33799793 · DOI 10.3390/cancers13061235
5. The Crosstalk between Autophagy and Nrf2 Signaling in Cancer: from Biology to Clinical Applications.
   Shan C, Wang Y, Wang Y. · · 2024 · cited 27× · PMID 39664581 · DOI 10.7150/ijbs.103187
6. Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.
   Hassan AMIA, Zhao Y, Chen X, He C. · · 2024 · cited 26× · PMID 39000565 · DOI 10.3390/ijms25137459
7. The role of autophagy in cancer: from molecular mechanism to therapeutic window.
   Jalali P, Shahmoradi A, Samii A, Mazloomnejad R, et al · · 2025 · cited 22× · PMID 40248706 · DOI 10.3389/fimmu.2025.1528230
8. Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance.
   Leonardo-Sousa C, Carvalho AN, Guedes RA, Fernandes PMP, et al · · 2022 · cited 21× · PMID 35408601 · DOI 10.3390/molecules27072201