Phase 2 Trial of Ixazomib Combinations in Patients With Relapsed Multiple Myeloma
This phase II trial studies how well ixazomib citrate works in treating patients with multiple myeloma that has returned after a period of improvement (relapsed) but is not resistant to bortezomib (refractory). Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
• Calculated creatinine clearance (using Cockcroft-Gault equation) \>= 30 mL/min (obtained =\< 14 days prior to registration)
• Absolute neutrophil count \>= 1000/mL (obtained =\< 14 days prior to registration)
• Untransfused platelet count \>= 75000/mL (obtained =\< 14 days prior to registration)
• Hemoglobin \>= 8.0 g/dL (obtained =\< 14 days prior to registration)
• Total bilirubin =\< 1.5 x the upper limit of the normal range (ULN) (obtained =\< 14 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN (obtained =\< 14 days prior to registration)
• Patients with relapsed multiple myeloma who have already received one or more standard treatment regimens
• Measurable disease of multiple myeloma as defined by at least ONE of the following:
‣ Serum monoclonal protein \>= 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
⁃ For patients with extramedullary disease (EMD) measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) or the CT portion of the positron emission tomography (PET)/CT: Must have at least one lesion that has a single diameter of \>= 2 cm. Skin lesions can be used if the area is \>= 2 cm in at least one diameter and measured with a ruler
⁃ Plasma cell count \>= 0.5 x 10\^9/L or 5 percent of the peripheral blood white cells
⁃ Plasma cell count if determined by flow cytometry, \>= 200/150,000 events
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2
• Provide informed written consent
• Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
• Willing to return to consenting Mayo Clinic institution for follow-up during the Active Monitoring Phase of the study; Note: during the Active Monitoring Phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
• Recovered (i.e., \< grade 1 toxicity) from the reversible effects of prior antineoplastic therapy
• Arms A - D only: Patients should be proteasome inhibitor naive (including bortezomib and carfilzomib) OR have received less than 6 cycles of therapy with a bortezomib or carfilzomib containing regimen and were not refractory to the bortezomib or carfilzomib based regimen (less than a PR or progression on or within 60 days of discontinuation)
• Arm E only: Negative hepatitis B test (defined by a negative test for hepatitis B surface antigen \[HBsAg\], or antibodies to hepatitis B surface and/or core antigens \[antiHBs or antiHBc\]) (added as of addendum 9); Note: patients with serologic findings suggestive of hepatitis B virus (HBV) vaccination (antiHBs positivity as the only serologic marker) AND a known history of prior HBV vaccination do not need to be tested for HBV deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR); those who are PCR positive will be excluded