Alternating Ixazomib Citrate and Lenalidomide as Maintenance Therapy After Stem Cell Transplant in Treating Patients With Multiple Myeloma

Female patients who are lactating or have a positive serum pregnancy test during the screening period

Failure to have fully recovered (i.e., =\< grade 1 toxicity) from the reversible effects of prior ASCT chemotherapy

Major surgery within 14 days before enrollment

Radiotherapy within 14 days before enrollment; if the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib

History of central nervous system multiple myeloma involvement

Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment

Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months

Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of cytochrome P450, family 1, subfamily A, polypeptide 2 gene (CYP1A2) (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P450, family 3, subfamily A gene locus (CYP3A) (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort

Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive

Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol

Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent; patient cannot be allergic to boron

Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing

Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease; patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection

Patient has \>= grade 2 peripheral neuropathy, or grade 1 with pain on clinical examination during the screening period

Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial

Patients with history prior to transplant of progression on lenalidomide therapy

What this study is about