Disulfiram and Copper Gluconate for the Treatment of Recurrent or Refractory Multiple Myeloma

Inclusion Criteria

• Male or female subject aged >= 18 years
• Relapsed or refractory myeloma that fits or did fit IMWG diagnostic criteria 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 magnetic resonance imaging (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
• Subjects have received 3 or more standard of care regimens including an immunomodulatory drug (lenalidomide, pomalidomide), proteasome inhibitor (bortezomib, carfilzomib, ixazomib), and an anti-CD38 monoclonal antibody (daratumumab, isatuximab), if available, and are relapsed and/or refractory to or intolerant of each regimen, with documented evidence of disease progression (per International Myeloma Working Group (IMWG) criteria) and must not be eligible for treatment with other regimens known to provide clinical benefit, as determined by the investigator. Subjects who have received a prior autologous bone marrow transplant, a B-cell maturation antigen (BCMA) directed therapy including bispecific T-cell engager, chimeric antigen receptor (CAR) T-cell, or antibody-drug conjugate, or allogeneic stem cell transplant are eligible for this study
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 or Karnofsky >= 60% * Note: Patients with lower performance status based solely on symptoms secondary to multiple myeloma are eligible
• Absolute neutrophil count (ANC) >= 1000/uL
• Platelet count >= 50,000/uL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x 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 Common Terminology Criteria for Adverse Events (CTCAE) version (v)5 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 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
• Grade >= 2 peripheral neuropathy
• 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 human immunodeficiency virus (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 tuberculosis [TB] testing in line with local practice), hepatitis B (known positive hepatitis B virus [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 hepatitis B surface antigen [HBsAg]) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (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