Cyclophosphamide, Bortezomib, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma

DISEASE CHARACTERISTICS:

Confirmed diagnosis of symptomatic multiple myeloma

Durie Salmon stage 2 or higher
Previously untreated multiple myeloma (including immunomodulatory drugs such as thalidomide) with the exception of bisphosphonates

Evaluable or measurable disease, as defined by at least one of the following:

Serum monoclonal protein ≥ 1 g/dL (measurable disease)
Urine monoclonal protein ≥ 200 mg/24 hours by protein electrophoresis (measurable disease)
Serum-free light chains (FLC) ≥ 10 mg/dL, kappa or lambda, accompanied by an abnormal kappa/lambda ratio

Serum FLC's should only be used for patients without measurable serum or urine m-spike

- Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease)

* Patients diagnosed with smoldering myeloma or monoclonal gammopathy of undetermined significance are not eligible

PATIENT CHARACTERISTICS:

Inclusion criteria:

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2

- ECOG PS of 3 will be allowed if secondary to pain in the opinion of the Investigator

Total bilirubin normal OR direct bilirubin ≤ 2.0 mg/dL
Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
AST ≤ 3 times ULN
Creatinine ≤ 3.5 mg/dL
Absolute neutrophil count ≥ 1,000/mm³ without transfusion or growth factor
Platelet count ≥ 100,000/mm³ without transfusion or growth factor
Willingness and the physical and mental capability to provide written informed consent
Willingness to return to Mayo Clinic Arizona/Princess Margaret Hospital for follow-up
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

Exclusion criteria:

Peripheral sensory neuropathy ≥ grade 2 as defined by National Cancer Institute (NCI) Common Terminology for Common Adverse Events (CTCAE) version 3.0
Known hypersensitivity to compounds containing boron or mannitol
Active uncontrolled infection

Severe cardiac comorbidity including but not limited to:

New York Heart Association class III or IV heart failure
History of myocardial infarction within the past 6 months
Uncontrolled angina or electrocardiographic (ECG) evidence of acute ischemia
Severe uncontrolled ventricular arrhythmias or ECG evidence of active conduction system abnormalities
Cardiac amyloidosis with hypotension (i.e., systolic blood pressure < 100 mm Hg)
Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent study compliance or completion of study treatment

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Prior high-dose corticosteroid therapy for 12 days or less is permitted for emergent complications from newly diagnosed multiple myeloma
More than 14 days since prior investigational agents

No concurrent steroids or any other anticancer agents or treatments

- Patients may receive the equivalent of up to 20 mg prednisone per day for concurrent illness or adrenal replacement therapy

Concurrent palliative radiotherapy for bony pain or fracture is allowed