Inclusion Criteria:
* Must be able to understand and voluntarily sign an informed consent form (ICF).
* Must be ≥ 18 years of age at the time of signing the ICF
* Must be able to adhere to the study visit schedule and other protocol requirements.
* Relapsed and/or refractory MM with:
* Documented evidence of progressive disease (PD) after achieving at least stable disease (SD) for ≥ 1 cycle during a previous MM treatment (i.e., relapsed MM). OR Disease progression during or within 60 days from the end of the most recent MM treatment (i.e., refractory MM).
* Previously undergone treatment with at least one immunomodulatory drug (lenalidomide or pomalidomide), one proteasome inhibitor (bortezomib, ixazomib, carfilzomib) and one anti-CD38 drug (daratumumab or isatuximab). These drugs could have been used in separate regimens or in combination.
* No effective standard of care options available
* Patients with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met:
* transplant was \> 12 weeks prior to study enrolment
* no active infection
* Patients with measurable disease defined as at least one of the following (these baseline laboratory studies for determining eligibility must be obtained within 28 days prior to start of study drug):
* Serum M-protein ≥ 0.5 g/dl (≥ 5 g/l)
* Urine M-protein ≥ 200 mg/24 h
* Serum free light chains (FLC) assay: Involved FLC level ≥ 10 mg/dl (≥ 100 mg/l) and an abnormal serum free light chain ratio (\< 0.26 or \> 1.65)
* If the serum protein electrophoresis is unreliable for routine M-protein measurement, quantitative immunoglobulin levels on nephelometry or turbidometry will be followed.
* Must have Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2.
* Females of child-bearing potential (FCBP) must have a negative serum pregnancy test and must either commit to continued abstinence from heterosexual intercourse or must abide by birth control requirements as described.
* Men with a female partner of childbearing potential must agree to use effective contraception from the time of first dose of study until 90 days after the last dose of study treatment to allow for clearance of any altered sperm.
* Able to take oral medications
* All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5) must be ≤Grade 1 at the time of enrollment except for alopecia or be deemed to be irreversible (for example, steroid induced cataracts or peripheral neuropathy).
* The following laboratory results must be met within 7 days of first study drug administration:
* Absolute neutrophil count (ANC) \>1000 cells/dL (1.0 x 10\^9/L). Growth factors cannot be given within 7 days of study drug administration.
* Serum AST and ALT ≤ 3 x upper limit of normal (ULN).
* Creatinine clearance ≥ 20 mL/min either directly measured via 24-hour urine collection or calculated using Cockroft-Gault
* Platelet count ≥ 50 x 109/L. For patients with \> 50% myeloma involvement in the marrow, a platelet count of ≥30 x 109/L is allowed. Patients may not have received a platelet transfusion within 72 hours prior to the platelet count used for eligibility
* Hemoglobin ≥ 80 g/L. Patients may receive red blood cell (RBC) transfusions in accordance with institutional guidelines to meet this criterion. Patients may not have received a red blood cell (RBC) transfusion within 72 hours prior to the hemoglobin result used for eligibility; use of growth factors is allowed.
* Total bilirubin ≤ 1.5 x ULN, unless known to have Gilbert's disease.
* Albumin ≥ 2.0 g/dL (20 g/L).
* Calcium \<1.2xULN.
Exclusion Criteria:
* Known history of clinically active amyloidosis, POEMS syndrome, or patients with plasma cell leukemia defined as circulating plasma cell count exceeding 500/uL or 5% of the peripheral blood white cells at the time of screening
* Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with patient's safety, obtaining informed consent or compliance to the study procedures.
* Pregnant or lactating females.
* Patients with previous or concurrent malignancies are allowed only if the second tumor is not contributing to the patient's illness. The patient must not be receiving active therapy, other than hormonal therapy for this disease and the disease must be considered medically stable for at least 2 years. The following are allowed:
* Adequately treated in situ carcinoma of the cervix uteri or the breast;
* Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
* In situ malignancy;
* Prostate cancer Gleason grade 6 or lower AND with stable Prostate Specific Antigen levels off treatment;
* Previous malignancy with no evidence of disease confirmed and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study.
* Evidence of cardiovascular risk including any of the following:
* QTc interval ≥ 470 msecs.
* Evidence of current clinically significant uncontrolled arrhythmias; including clinically significant ECG abnormalities; including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block.
* History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening.
* Class III or IV heart failure as defined by the New York Heart Association functional classification system
* Uncontrolled hypertension
* Ejection fraction \<40% as determined by echocardiogram
* Active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Presence of hepatitis B surface antigen (HBsAg) or positive HBV PCR test at screening or within 3 months prior to first dose of study treatment. Participants with positive hepatitis B core antibody (HBcAb) can be enrolled, only if confirmatory negative Hepatitis B DNA is obtained AND patient is on hepatitis B prophylaxis (e.g. tenofovir or entecavir) before first dose of study drugs. Presence of isolated Hep B surface antibody (HBsAb) indicating previous vaccination will not exclude a participant. Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment. Note: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. Hepatitis RNA testing is optional and participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing. Patients with HIV with detectable viral load or with AIDS-defining features or illnesses will be excluded.
* Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator's assessment).
* Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal or cardiac disease).
* Current or past history of clinically significant CNS disease, such as stroke, epilepsy, CNS vasculitis, neurodegenerative disease, or CNS involvement by MM
* Note that patients with a history of stroke who have not experienced a stroke or transient ischemic attack in the past 2 years and have no residual neurologic deficits as judged by the investigator are allowed.
* Note that patients with a history of epilepsy who have had no seizures in the past 2 years while not receiving any anti-epileptic medications are allowed.
* Known active infection requiring treatment.
* Receiving systemic immunosuppressive medications (including, but not limited to, azathioprine, methotrexate, and anti-tumor necrosis factor agents), with the exception of corticosteroid treatment \<10mg/day prednisone or equivalent within 2 weeks. Inhaled corticosteroids for respiratory diseases are allowed.
* Evidence of active mucosal or internal bleeding.
* Significant urinary outflow obstruction
* Radiotherapy or systemic therapy (standard or biologic anticancer agent) within 14 days of initiation of study drug treatment.
* Use of an investigational drug within 21 days or five half-lives, whichever is shorter, preceding the first dose of study drug.
* Major surgery within 28 days
* Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to liposomal curcumin.
