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

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Thalidomide may stop the growth of cancer cells by blocking blood flow to the tumor. Giving combination chemotherapy together with carfilzomib and thalidomide may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of carfilzomib when given together with cyclophosphamide, thalidomide, and dexamethasone in treating patients with newly diagnosed active multiple myeloma.

PRIMARY OBJECTIVES:

I. To establish the maximum tolerated dose of carfilzomib given in combination with oral cyclophosphamide and thalidomide and dexamethasone. (Phase I) II. In newly diagnosed myeloma to evaluate the response rate (CR, nCR, and VGPR) to carfilzomib given in combination with oral cyclophosphamide and thalidomide and dexamethasone after four 28 day cycles. (Phase II)

SECONDARY OBJECTIVES:

I. Determine the overall response rate (CR, nCR, PR) after 4, 8, 12 cycles. II. Determine the duration of progression-free and overall survival for patients receiving this regimen.

III. To evaluate the incidence of toxicities for this regimen. IV. To evaluate the ability to successfully collect peripheral blood stem cells following four months of combination therapy.

OUTLINE: This is a phase I, dose escalation study of carfilzomib followed by a phase II study.

Patients receive carfilzomib IV on days 1, 2, 8, 9, 15, and 16; oral cyclophosphamide on days 1, 8, and 15; oral dexamethasone on days 1, 8, 15, and 22; and oral thalidomide on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 3 months, then every 3 months for 1 year, and then every 6 months for up to 3 years.

Eligibility Criteria:
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