| Eligibility |
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;
- 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.
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
- 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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