Inclusion Criteria

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not part of normal medical care, with the understanding that consent may be withdrawn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