Aurora A Kinase Inhibitor MLN8237 and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma

Inclusion

* ANC \>= 1500/uL
* AST =\< 2.5 x ULN
* Creatinine =\< 1.5 x ULN
* Creatinine clearance as calculated by the method of Cockroft and Gault \>= 30 mL/minute
* Patients with relapsed or refractory multiple myeloma requiring treatment
* Patients who have received prior bortezomib therapy will be allowed on trial as long as they did not progress during bortezomib or =\< 60 days of therapy discontinuation
* Negative serum pregnancy test done =\< 7 days prior to registration, for women of childbearing potential (WOCBP) only (a WOCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months)
* Willingness to return to enrolling institution for follow-up
* Life expectancy \>= 12 weeks
* Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
* Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
* Male subject agrees to use an acceptable method for contraception for the duration of the study
* Patients have a baseline LVEF \>= 45% at baseline
* Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
* PLT \>= 100,000/uL
* Total bilirubin =\<1.5 x upper limit of normal (ULN) or if total bilirubin is \> 1.5 x ULN, the direct bilirubin must be =\< 2.0 mg/dL
* 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, monoclonal bone marrow plasmacytosis \>= 30% (evaluable disease), or measurable plasmacytoma
* ECOG Performance Status (PS) 0, 1, or 2
* Hgb \>= 9 g/dl

Exclusion

* Major surgery, open biopsy (excluding bone marrow) or significant traumatic injury =\< 4 weeks prior to registration
* Melphalan or other myelosuppressive agents including lenalidomide and non-myelosuppressive agents such as thalidomide or high dose corticosteroids =\< 2 weeks prior to registration
* Concurrent use of corticosteroids, but patients may be on chronic steroids (maximum dose 20 mg/day prednisone equivalent) if they are being given for disorders other than myeloma, i.e., adrenal insufficiency, rheumatoid arthritis, etc
* Uncontrolled infection
* Pregnant women or women of reproductive ability who are unwilling to use effective contraception
* Nursing women
* Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 4 weeks after stopping treatment
* Other co-morbidity or psychiatric illness which would interfere with patient's ability to participate in this trial
* Recent history of myocardial infarction in the six months prior to registration
* Uncontrolled angina or electrocardiographic evidence of acute ischemia
* Severe uncontrolled ventricular arrhythmias or electrocardiographic evidence of active conduction system abnormalities
* Cardiac amyloidosis with hypotension (systolic BP less than 100mmHg)
* MGUS or smoldering myeloma
* Serious non-healing wound, or ulcer
* Known hypersensitivity to Bortezomib, boron or mannitol
* Patient has \>=Grade 2 peripheral neuropathy within 14 days before enrollment
* Patient has received other investigational drugs with 14 days before enrollment
* Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
* Infection requiring systemic antibiotic therapy within 14 days preceding the first dose of study drug, or other severe infection
* Inability to swallow orally administered medication
* Prior allogeneic bone marrow or organ transplantation
* Patients who are currently receiving digoxin, cyclosporine, tacrolimus or sirolimus
* Severe cardiac comorbidity
* Known positive for HIV or active infectious hepatitis, type A, B or C