Cyclophosphamide, Carfilzomib, Thalidomide, and Dexamethasone in Treating Patients With Newly Diagnosed Active Multiple Myeloma

Inclusion

* Creatinine =\< 2 mg/dL
* Calculated Creatinine Clearance \>= 30 mL/min
* Total Bilirubin =\< 2.0 mg/dL
* Alkaline Phosphatase =\< 3 x ULN
* ALT =\< 3 x ULN
* Absolute neutrophil count \>= 1000/uL
* Platelet \>= 75000/uL
* Hemoglobin \>= 8.0 g/dL
* Untreated symptomatic myeloma: Prior non-systemic therapy for the treatment of solitary plasmacytoma is permitted, but \>= 1 month should have elapsed from the last day of radiation; prior therapy with clarithromycin, DHEA, anakinra, pamidronate or zoledronic acid is permitted; any additional agents not listed must be approved by the Principal Investigator
* Prior high dose corticosteroid therapy for twelve days (480 mg total dose) or less is permitted for emergent complications from newly diagnosed multiple myeloma
* Measurable disease of multiple myeloma, as defined by at least ONE of the following:
* Serum monoclonal protein \>= 1.0 g by protein electrophoresis
* OR \> 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
* OR serum immunoglobulin free light chain \>= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio; OR monoclonal bone marrow plasmacytosis \>= 30% (evaluable disease)
* ECOG performance status (PS) 0, 1, 2; ECOG PS of 3 will be allowed if secondary to pain in the opinion of the Investigator
* Willingness and able to provide informed written consent
* Negative serum pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
* Willingness to return to Mayo Clinic enrolling institution for follow-up

Exclusion

* MGUS or smoldering myeloma
* Peripheral sensory neuropathy \>= Grade 2 as defined by CTEP Active Version of the CTCAE
* Active malignancy with the exception of non melanoma skin cancer or in situ cervical or breast cancer
* 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
* Known hypersensitivity, allergy or inability to tolerate any of the agents employed
* Active, uncontrolled infection
* Severe cardiac comorbidity
* New York Heart Association Class III or IV Heart Failure
* 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 100 mmHg)
* Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
* The following medications are not permitted during the trial: any other investigational treatment; any cytotoxic chemotherapy; any other systemic anti-neoplastic therapy including, but not limited to, immunotherapy, hormonal therapy, or monoclonal antibody therapy
* Palliative radiation therapy is permitted if clinically indicated and not indicative of progressive disease