Pembrolizumab, Ixazomib Citrate, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma

Inclusion Criteria

• Diagnosis of relapsed, symptomatic multiple myeloma by International Myeloma Working Group (IMWG) diagnostic criteria for multiple myeloma
• Age >= 18 years
• Calculated creatinine clearance (using Cockcroft-Gault equation below) >= 30 mL/min (obtained = = 1000/mm^3 (obtained = = 75000/mm^3; Note: Platelet transfusion is not allowed = = 8.0 g/dL (obtained = = 1.0 g/dL
• >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
• Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, or 1
• Provide informed written consent
• Negative pregnancy test done = = grade 3 on clinical examination or grade 2 with pain during the screening period
• Major surgery =< 14 days prior to study registration
• Radiotherapy =< 14 days prior to registration; NOTE: If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of study drugs
• Participation in any other clinical trials with other investigational agents not included in this trial =< 21 days prior to registration
• Has active autoimmune disease that has required systemic treatment =< 2 years prior to study registration (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs);
• NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Has a known history of interstitial lung disease
• Has an active infection requiring systemic therapy
• Has a history of current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
• Has a known history of active TB (Bacillus tuberculosis)
• Has received a live vaccine =< 30 days prior to study registration
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Allogeneic hematopoietic stem cell transplant
• Systemic treatment with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort =< 14 days prior to registration
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing