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Multiple MyelomaPhase 1MYELOMA-HCQNCT04163107

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

A Phase 1 study testing Hydroxychloroquine, Carfilzomib Injection and Dexamethasone in people with Multiple Myeloma, run by Norwegian University of Science and Technology at 2 sites in Norway.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Hydroxychloroquine, Carfilzomib Injection and Dexamethasone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
2 sitesNorway
Study dates
7 Jan 2020to 28 Dec 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Demographic and diagnosis
  • A prior diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) criteria with documented disease progression in need of treatment at time of screening.
  • Must meet all of the following criteria:
  • Patients must have received at least two prior therapies including bortezomib and an immunomodulatory agent (may include autologous bone marrow transplantation)
  • Patients must not be refractory to carfilzomib
  • Relapsed or progressive disease documented according to IMWG criteria
Show all 62Show fewer
  • Patients must have evaluable multiple myeloma with at least one of the following (assessed within 21 days prior to registration)
  • Serum M-protein ≥ 10 g/L, or
  • Urine M-protein ≥ 200 mg/24 hours
  • Involved serum immunoglobulin free light chain (SFLC) > 100 mg/L AND abnormal kappa/lambda ratio
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Life expectancy ≥ 6 months
  • Laboratory:
  • Absolute neutrophil count ≥ 1.0 x 109/L
  • Hemoglobin ≥ 7 g/dL (with or without transfusion support)
  • Platelets ≥ 50 x 109/L (with or without transfusion support)
  • Total bilirubin ≤ 2 x upper limit of normal (ULN)
  • Aspartate amino transferase/alanine amino transferase ratio (ASAT/ALAT) ≤ 2.5 x ULN
  • Creatinine ≤ 2 x ULN
  • Concurrent conditions
  • Left ventricular ejection fraction (LVEF) ≥ 40 % determined by 2D transthoracic echocardiogram (ECHO) or Multigated Acquisition Scan (MUGA)
  • No baseline peripheral neuropathy ≥ grade 2
  • No history of allergic reactions to compounds of similar chemical or biological composition to carfilzomib, dexamethasone or hydroxychloroquine, including Captisol (a cyclodextrin derivate used to solubilize carfilzomib)
  • No macular degeneration or retinopathy (diabetic or otherwise) as examined during screening, or known porphyria or psoriasis (with the exception of early dry age-related macular degeneration or minor microhemorrhages in the retinal periphery)
  • Well-controlled psoriasis allowed under care of a specialist who agrees to monitor the patient for exacerbations
  • No other condition that would require therapy with hydroxychloroquine, including but not limited to, any of the following:
  • Systemic lupus erythematosus
  • Rheumatoid arthritis
  • Porphyria cutanea tarda
  • Malaria treatment or prophylaxis
  • No concurrent or prior malignancy except for the following:
  • Basal cell or squamous cell carcinoma of the skin
  • Treated carcinoma in situ
  • Localized prostate adenocarcinoma (stage T1a or T1b) with a stable prostate-specific antigen (PSA) for a period fo at least 4 months allowed
  • Patients with a prior malignancy treated with chemotherapy, biologic agents, and/or radiation are eligible for this study if they have completed therapy ≥ 2 years previously with no evidence of recurrent disease
  • Patients with a prior malignancy treated with surgery alone are eligible for this study if they have completed therapy ≥ 2 years previously with no evidence of recurrent disease
  • No uncontrolled intercurrent illness including, but not limited to, any of the following:
  • Uncontrolled ongoing infection
  • Known acute or chronic hepatitis B, active hepatitis A or C or human immunodeficiency virus (HIV)
  • Symptomatic congestive heart failure, defined as New York Heart Association (NYHA) Class III or IV
  • Unstable angina pectoris
  • Myocardial infarction within 6 months of enrollment
  • Cardiac arrhythmia
  • Clinically significant pericardial disease
  • Cardiac amyloidosis
  • Severe lung disease
  • Psychiatric illness or social situations that would prevent compliance with study requirements
  • Prior and concurrent therapy
  • No prior dose reductions of carfilzomib administration in previous lines
  • At least 14 days since prior antimyeloma agents, not including carfilzomib/dexamethasone
  • Concurrent therapy with bisphosphonates allowed at the discretion of the treating physician
  • Concurrent hematopoetic growth factors allowed, including filgrastim granulocyte colony-stimulating factor (G-CSF) or pegfilgrastim, epoetin alpha, and darbepoetin alpha
  • Concurrent participation in non-treatment studies allowed, if it will not interfere with participation in this study
  • No concurrent radiotherapy except local radiotherapy during the treatment phase of this study for palliation of pain or prevention of fracture
  • No concurrent treatment with a different investigational regimen
  • No concurrent treatment with other anticancer agents
  • No concurrent participation in other investigational trials that involve novel therapies
  • Ethical/other
  • Female patients of child-bearing potential (FCBP) must have negative serum pregnancy test within 21 days prior to registration and agree to use an effective method of contraception during and for 3 months following last dose of drug.
  • Male patients must use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with a FCBP.
  • Ability to understand and willingness to sign the informed consent document
  • Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-GCP), and national/local regulations.

Who cannot join

  • Not meeting inclusion criteria
  • Female patients who are pregnant or lactating.
  • Any reason why, in the opinion of the investigator, the patient should not participate (e.g. not able to comply with study procedures, including being unable to perform full ophthalmologic examination).

Trial locations and contacts

2 sites in 1 country.

Norway2 sites

  • Oslo University Hospital, Department of Hematology, Oslo Myeloma Center

    Oslo

  • St. Olavs Hospital, Department of Hematology

    Trondheim

Other trials in Norway

About this study

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

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.

Being tested
Hydroxychloroquine, Carfilzomib Injection, Dexamethasone
Keywords
Drug Therapy, Administration and Dosage, Hydroxychloroquine, Carfilzomib, Dexamethasone, Drug Therapy, Combination
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HydroxychloroquineDrug

    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.

  • Carfilzomib InjectionDrug

    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.

  • DexamethasoneDrug

    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.

Study groups in NCT04163107
Study groupRoleWhat they receive
Combination treatment of carfilzomib/dexamethasone/HCQExperimentalNot described
Receives: Drug: Hydroxychloroquine; Drug: Carfilzomib Injection; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. maximum tolerated dose of hydroxychloroquine when added to standard-dose regimen of carfilzomib/dexamethasone

    Measured: 3 months

Secondary outcomes (1)

  1. estimate of toxicity rate of hydroxychloroquine when added at a maximum tolerated dose to standard-dose regimen of carfilzomib/dexamethasone

    Measured: 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Nov 2019
  2. Study start7 Jan 2020
  3. Primary completion28 Dec 2021
  4. Study completion28 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
A single arm, dose escalation study in two centers. 3+3 design in five dose levels.
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04163107
Sponsor's protocol ID
2019/922
Other IDs
2019-000986-19, 2019
Acronym
MYELOMA-HCQ
Status last verified
Mar 2022
First submitted
11 Nov 2019
Last updated
18 Mar 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: tba

Publications

  • Slordahl TS, Askeland FB, Hanssen MSS, Hov H, Sundt-Hansen SM, Lindahl S, Vethe NT, Hjorth-Hansen H, Fenstad MH, Waage A, Hjertner O, Schjesvold F, Sundan A. Combined Proteasome and Autophagy Inhibition in Relapsed/Refractory Multiple Myeloma-A Phase I Trial of Hydroxychloroquine, Carfilzomib, and Dexamethasone. EJHaem. 2025 Jan 23;6(1):e1091. doi: 10.1002/jha2.1091. eCollection 2025 Feb.

    PubMed 39866949

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Hydroxychloroquine, Carfilzomib Injection and Dexamethasone in people with Multiple Myeloma, run by Norwegian University of Science and Technology at 2 sites in Norway.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 62 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

maximum tolerated dose of hydroxychloroquine when added to standard-dose regimen of carfilzomib/dexamethasone (time frame: 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04163107, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2022.

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