Study of Disulfiram and Copper Gluconate in Patients With Treatment-Refractory Multiple Myeloma

NCT04521335 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: HCI131966
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• 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.

  time from cycle one day one until cycle two day one (28 days)

Study Arms (1)

Treatment: all patients

EXPERIMENTAL

disulfiram and copper gluconate in combination

Drug: Disulfiram; Drug: Copper Gluconate

Interventions

Disulfiram DRUG

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.

Treatment: all patients

Copper Gluconate DRUG

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.

Treatment: all patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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;
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• University of Utah: lead
• Cantex Pharmaceuticals: collaborator

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• 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.

  PMID: 35285015 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Disulfiram; Gluconates

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ditiocarb; Thiocarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Disulfides; Sulfides; Sulfur Compounds; Sugar Acids; Hydroxy Acids; Carbohydrates

Study Officials

• Douglas Sborov, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 18, 2020
• First Posted: August 20, 2020
• Study Start: May 21, 2021
• Primary Completion: December 9, 2021
• Study Completion: February 6, 2022
• Last Updated: March 13, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)