Multiple MyelomaPhase 1Repurpose-1NCT04521335
Study of Disulfiram and Copper Gluconate in Patients With Treatment-Refractory Multiple Myeloma
A Phase 1 study testing Disulfiram and Copper Gluconate in people with Multiple Myeloma, run by University of Utah at 1 site in United States.
Trial summary
This is a phase I, open-label trial of disulfiram in combination with copper gluconate in patients with treatment-refractory multiple myeloma. The trial is designed to assess the Phase 2 Recommended Dose (RP2D) of disulfiram and copper gluconate in combination. 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?
- Disulfiram and Copper Gluconate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 21 May 2021to 6 Feb 2022
- 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
- Male or female subject aged ≥ 18 years.
- Relapsed or refractory myeloma that fits or did fit IMWG diagnostic criteria1 for symptomatic myeloma (although new or worsening end organ damage is not required to be eligible) as defined below:
- Presence of > 10% clonal bone marrow plasma cells and/or biopsy-proven extramedullary plasmacytoma;
- Evidence of myeloma defining event(s) attributed to the patient's myeloma:
- Hypercalcemia: Serum calcium > 11.5 mg/dL; or
- Renal Insufficiency: Serum creatinine > 2 mg/dL; or
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- Anemia > 2 g/dL below the lower limit of normal or hemoglobin value < 10 g/dL; or
- Bone lesions: lytic lesions, severe osteopenia, pathologic fractures, or > 1 lesion on MRI at least 5 mm in size;
- Bone marrow plasma cells > 60%
- Serum free light chain ratio > 100
- Expansion cohort only: patients must have measurable disease defined as any of the following:
- Serum monoclonal protein > 500 mg/dL by protein electrophoresis;
- 200 mg of monoclonal protein in the urine on screening 24-hour electrophoresis;
- Serum immunoglobulin free light chain > 100 mg/L AND abnormal serum immunoglobulin kappa to lambda free light chain ratio.
- Progressed during or after an immunomodulatory drug, proteasome inhibitor, and anti-CD38 antibody, and at least 2 prior lines of therapy.
- ECOG performance status ≤ 2 or Karnofsky ≥ 60% (Appendix 1). --Note: Patients with lower performance status based solely on symptoms secondary to multiple myeloma are eligible.
- Adequate organ function as defined as:
- --Hematologic:
- ANC ≥ 1000 /μL
- Platelet count > 50,000 /μL
- --Hepatic:
- Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
- AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN
- Normal serum copper levels and serum ceruloplasmin > 17 mg/dL.
- No known allergy to disulfiram or copper.
- Willing to refrain from ingestion of alcoholic beverages while in the study.
- Negative serum or urine pregnancy test at screening for women of childbearing potential ≤ 14 days prior to cycle one day one.
- Highly effective contraception for both male and female subjects throughout the study and for at least 14 days after last study treatment administration if the risk of conception exists.
- Recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
- Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
Who cannot join
- Prior autologous and/or allogeneic transplant and/or CAR-T cell occurred ≤ 90 days prior to registration.
- Prior chemotherapy ≤ 2 weeks prior to the first dose of study treatment.
- Requires systemic corticosteroid therapy > 10 mg daily of prednisone or its equivalent for the management of symptoms or comorbid conditions.
- --Note: Doses of corticosteroid should be ≤ 10 mg prednisone or equivalent and stable for at least 7 days prior to starting study treatment to be deemed eligible.
- Receiving any other therapeutic investigational agents.
- Active treatment with any herbal or dietary supplements
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- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
- --Cardiovascular disorders:
- Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
- Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 6 months before the first dose.
- Left ventricular ejection fraction < 45% (only to be assessed at screening if clinically indicated).
- History of seizures, psychosis, or schizophrenia.
- History of liver disease, Wilson's disease, or hemochromatosis.
- Known HIV infection with a detectable viral load at the time of screening.
- --Note: Patients on effective antiretroviral therapy with an undetectable viral load at the time of screening are eligible for this trial.
- Active or ongoing infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), or hepatitis C.
- --Note: Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes (POEMS) syndrome.
- Concurrent use of complementary or alternative medicines that in the opinion of the principal investigator would confound the interpretation of toxicities and/or antitumor activity of the study drug.
- Live attenuated vaccinations within ≤ 4 weeks of the first dose of study therapy.
- Known prior severe hypersensitivity to investigational product or any component in its formulations (NCI CTCAE v5.0 Grade ≥ 3) including a history of rubber contact dermatitis for hypersensitivity to thiuram derivatives.
Trial locations and contacts
1 site in 1 country.
United States1 site
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
About this study
Official title: A Phase I Study of Disulfiram and Copper Gluconate in Patients With Treatment-Refractory Multiple Myeloma
This is a phase I, open-label trial of disulfiram in combination with copper gluconate in patients with treatment-refractory multiple myeloma. The trial is designed to assess the Phase 2 Recommended Dose (RP2D) of disulfiram and copper gluconate in combination. The trial will open with dose escalation, followed to an expansion cohort to further characterize the safety and tolerance of the combination.
Dose escalation will utilize a standard 3+3 design and will test up to five dose levels. Dose levels will be separated into two sequential parts defined by the fixed dose of copper as copper gluconate administered with ascending doses of disulfiram. Part 1 of dose escalation will consist of dose levels 0 and 1 with the option to reduce to Dose Level -1 if Dose Level 0 is deemed intolerable. Part 2 will test dose levels 2 and 3. The Dose Level deemed to be the RP2D will be used in dose expansion.
- Conditions
- Multiple Myeloma
- Being tested
- Disulfiram, Copper Gluconate
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DisulfiramDrug
Patients will be instructed to self-administer disulfiram and copper gluconate twice daily at the assigned dose level. Both medications will be administered in 28-day cycles.
Copper GluconateDrug
Patients will be instructed to self-administer disulfiram and copper gluconate twice daily at the assigned dose level. Both medications will be administered in 28-day cycles.
| Study group | Role | What they receive |
|---|---|---|
| Treatment: all patients | Experimental | disulfiram and copper gluconate in combination Receives: Drug: Disulfiram; Drug: Copper Gluconate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of dose limiting toxicities (DLTs) during the DLT evaluation period.
assess the recommended phase 2 dose of disulfiram in combination with copper as copper gluconate in subjects with relapse/refractory multiple myeloma.
Measured: time from cycle one day one until cycle two day one (28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2020
- Study start21 May 2021
- Primary completion9 Dec 2021
- Study completion6 Feb 2022
Why it stopped: Closed at PI's Request
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 standard 3+3 dose escalation design will be used to determine the recommended phase 2 dose (RP2D) while ensuring the safety and tolerability of the treatment. Once the RP2D has been assigned in dose-escalation, an expansion cohort will open to the enrollment of 14 additional patients to further characterize the safety and tolerability of the study intervention.
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- Cantex Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Douglas Sborov, MD, Principal investigator, Huntsman Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04521335
- Sponsor's protocol ID
- HCI131966
- Acronym
- Repurpose-1
- Status last verified
- Mar 2023
- First submitted
- 18 Aug 2020
- Last updated
- 13 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Saifi MA, Shaikh AS, Kaki VR, Godugu C. Disulfiram prevents collagen crosslinking and inhibits renal fibrosis by inhibiting lysyl oxidase enzymes. J Cell Physiol. 2022 May;237(5):2516-2527. doi: 10.1002/jcp.30717. Epub 2022 Mar 13.
PubMed 35285015
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Disulfiram and Copper Gluconate in Patients With Treatment-Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT04521335
- Acronym / sponsor ID
- Repurpose-1 / HCI131966
- Conditions
- Multiple Myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Closed at PI's Request
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- Cantex Pharmaceuticals
- Study start
- 21 May 2021 (actual)
- Primary completion
- 9 Dec 2021 (actual)
- Study completion
- 6 Feb 2022 (actual)
- First posted
- 20 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase I, open-label trial of disulfiram in combination with copper gluconate in patients with treatment-refractory multiple myeloma. The trial is designed to assess the Phase 2 Recommended Dose (RP2D) of disulfiram and copper gluconate in combination. The trial will open with dose escalation, followed to an expansion cohort to further characterize the safety and tolerance of the combination.
Dose escalation will utilize a standard 3+3 design and will test up to five dose levels. Dose levels will be separated into two sequential parts defined by the fixed dose of copper as copper gluconate administered with ascending doses of disulfiram. Part 1 of dose escalation will consist of dose levels 0 and 1 with the option to reduce to Dose Level -1 if Dose Level 0 is deemed intolerable. Part 2 will test dose levels 2 and 3. The Dose Level deemed to be the RP2D will be used in dose expansion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A standard 3+3 dose escalation design will be used to determine the recommended phase 2 dose (RP2D) while ensuring the safety and tolerability of the treatment. Once the RP2D has been assigned in dose-escalation, an expansion cohort will open to the enrollment of 14 additional patients to further characterize the safety and tolerability of the study intervention.
| Arm | Type | Receives |
|---|---|---|
| Treatment: all patients | Experimental | Drug: Disulfiram, Drug: Copper Gluconatedisulfiram and copper gluconate in combination |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- Male or female subject aged ≥ 18 years.
- Relapsed or refractory myeloma that fits or did fit IMWG diagnostic criteria1 for symptomatic myeloma (although new or worsening end organ damage is not required to be eligible) as defined below:
- Expansion cohort only: patients must have measurable disease defined as any of the following:
- Progressed during or after an immunomodulatory drug, proteasome inhibitor, and anti-CD38 antibody, and at least 2 prior lines of therapy.
- ECOG performance status ≤ 2 or Karnofsky ≥ 60% (Appendix 1). --Note: Patients with lower performance status based solely on symptoms secondary to multiple myeloma are eligible.
Key exclusion criteria (22 listed)
- Prior autologous and/or allogeneic transplant and/or CAR-T cell occurred ≤ 90 days prior to registration.
- Prior chemotherapy ≤ 2 weeks prior to the first dose of study treatment.
- Requires systemic corticosteroid therapy > 10 mg daily of prednisone or its equivalent for the management of symptoms or comorbid conditions.
- --Note: Doses of corticosteroid should be ≤ 10 mg prednisone or equivalent and stable for at least 7 days prior to starting study treatment to be deemed eligible.
- Receiving any other therapeutic investigational agents.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DisulfiramPatients will be instructed to self-administer disulfiram and copper gluconate twice daily at the assigned dose level. Both medications will be administered in 28-day cycles. | Drug | Treatment: all patients |
| Copper GluconatePatients will be instructed to self-administer disulfiram and copper gluconate twice daily at the assigned dose level. Both medications will be administered in 28-day cycles. | Drug | Treatment: all patients |
Primary outcome
Rate of dose limiting toxicities (DLTs) during the DLT evaluation period.
Time frame: time from cycle one day one until cycle two day one (28 days)
assess the recommended phase 2 dose of disulfiram in combination with copper as copper gluconate in subjects with relapse/refractory multiple myeloma.
Results and safety
The study was stopped early (reason given: Closed at PI's Request). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2023.
- Derived from this study: PubMed 35285015Saifi MA, Shaikh AS, Kaki VR, Godugu C. Disulfiram prevents collagen crosslinking and inhibits renal fibrosis by inhibiting lysyl oxidase enzymes. J Cell Physiol. 2022 May;237(5):2516-2527. doi: 10.1002/jcp.30717. Epub 2022 Mar 13.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Douglas Sborov, MD principal investigator
Huntsman Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Disulfiram and Copper Gluconate in people with Multiple Myeloma, run by University of Utah at 1 site in United States.
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 30 inclusion and 22 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: stopped early, as of the sponsor's last update on 13 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 was stopped early (reason given: Closed at PI's Request). Results are not available in the source record.
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?
Rate of dose limiting toxicities (DLTs) during the DLT evaluation period. (time frame: time from cycle one day one until cycle two day one (28 days)). 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 NCT04521335, 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 13 Mar 2023.