Study of Disulfiram and Copper Gluconate in Patients With Treatment-Refractory Multiple Myeloma (Repurpose-1)

  • STATUS
    Recruiting
  • End date
    Dec 10, 2025
  • participants needed
    38
  • sponsor
    University of Utah
Updated on 10 March 2022
platelet count
anemia
measurable disease
bone marrow procedure
refractory multiple myeloma
hypercalcemia

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.

Details
Condition Multiple Myeloma
Treatment Disulfiram, Copper gluconate
Clinical Study IdentifierNCT04521335
SponsorUniversity of Utah
Last Modified on10 March 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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
Adequate organ function as defined as
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
\--Hematologic
ANC ≥ 1000 /μL
Platelet count > 50,000 /μL
\--Hepatic
Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
Normal serum copper levels and serum ceruloplasmin > 17 mg/dL
AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN
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

Exclusion Criteria

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
eligible
and stable for at least 7 days prior to starting study treatment to be deemed
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
\--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
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