Mezigdomide Plus Ixazomib and Dexamethasone for Relapsed and Refractory Multiple Myeloma

Inclusion Criteria:

ECOG performance status < 2
Patients must have a confirmed diagnosis of multiple myeloma and have received 1-3 prior lines of therapy and must be:

Exposed to a proteasome inhibitor, IMiD, and anti-CD38 antibody prior to enrollment. Patients must have measurable evidence of multiple myeloma defined as one of the following:

Serum M protein ≥ 0.5 g/dL
Abnormal free light chain ratio, provided involved light chain is >10mg/dL
Urine M protein ≥ 200 mg/24 hours

Hematologic laboratory parameters of:

Absolute neutrophil count (ANC) > 1,000/mm3
Hemoglobin > 8g/dL
Platelet count > 75,000/μL if plasma cells account for < 50% bone marrow
Nucleated cells and > 50,000/μL if plasma cells account for > 50% of bone marrow nucleated cells

Non-hematologic laboratory parameters of:

Total Bilirubin of < 2 times the upper limit of normal
ALT and AST < 3 times the upper limit of normal
Corrected serum calcium >13 mg/dL
Estimated creatinine clearance (CrCl) of ≥ 45 mL/min, calculated using the formula of Cockroft and Gault (may need adjusted per mezigdomide pharmacokinetic report)
Access to ixazomib

Females of childbearing potential (FCBP) must:

o Have two negative pregnancy tests prior to starting study treatment and agree to ongoing pregnancy testing during the course of the study, and after end of study treatment.

All male and female participants must follow all requirements defined in the pregnancy prevention plan

Exclusion Criteria:

Central Nervous system involvement of multiple myeloma
Plasma cell leukemia defined as clonal plasma cells constituting > 20% of peripheral leukocyte differential
Waldenstrom's Macroglobulinemia, POEMS syndrome or Light Chain (AL) AmyloidosisF
Prior refractoriness to a proteasome inhibitor (bortezomib, carfilzomib, ixazomib), defined as documented progression within 60 days of a PI-containing regimen
Prior intolerance of ixazomib
Prior exposure to mezigdomide
Females with positive pregnancy test during screening or females who wish to become pregnant
Unwillingness to strictly adhere to the Pregnancy Prevention Plan
Concomitant or recent (within 2 weeks of starting study therapy) use of strong CYP3A modulators and proton pump inhibitors (PPIs)
Active cardiopulmonary conditions including documented myocardial ischemia within 6 months, unstable angina, congestive heart failure (New York Heart Association class III or IV), uncontrolled arrythmias, Grade 3 conduction block without a pacemaker, uncontrolled hypertension, baseline QTc >470ms or chronic obstructive pulmonary disease with FEV1 <50%
Any other malignancy diagnosed within 2 years of enrollment with documented or presumed residual disease, excluding non-melanomatous skin cancer if completely resected
Active bacterial or fungal infection requiring antimicrobial therapy (not standard prophylactic prophylaxis)
HIV, chronic or active hepatitis B, or active hepatitis A or C
Unwillingness to adhere to antithrombotic and antiviral prophylaxis
Major surgery within 30 days of enrollment
Radiotherapy within 14 days of initiating study treatment
Known allergy to any study compounds (mezigdomide, ixazomib)
Intolerance of dexamethasone
Documented gastrointestinal disease resulting reduced absorption of oral medications
Grade > 3 neuropathy
Active participation in another clinical trial or recent participation within 1 month of enrollment
Any medical or psychiatric condition interfere with the patient's ability to tolerate or complete this treatment protocol, as determined by principal investigator