Inclusion Criteria

Inclusion Criteria (Crit.):

1. Has a diagnosis of MM based on the following:

Major crit.:

1. plasmacytomas on tissue biopsy

2. bone marrow plasmacytosis (> 30% plasma cells)

3. m-spike on serum electrophoresis IgG > 3.5 g/dL or IgA > 2.0 g/dL; kappa or
lambda light chain excretion > 1 g/day on 24 hour urine protein electrophoresis

Minor crit.:

1. bone marrow plasmacytosis (10% to 30% plasma cells)

2. monoclonal Ig present but of lesser magnitude than given under major crit.

3. lytic bone lesions

4. normal IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL

Any of the following sets of crit. will confirm the diagnosis of MM:

- any 2 of the major crit.

- major criterion 1 plus minor criterion 2, 3, or 4

- major criterion 3 plus minor criterion 1 or 3

- minor crit. 1, 2, and 3, or 1, 2, and 4

2. MM with measurable disease, defined as:

- a m-spike on serum electrophoresis of at least 0.5 g/dL and/or

- urine monoclonal protein levels of at least 200 mg/24 hours

- for patients without measurable serum and urine M-protein levels, an abnormal
free light chain ratio (normal value: 0.26 - 1.65)

3. Currently has progressive MM:

- Relapsed following stabilization or a response to at least one IV bortezomib
(bort.) containing combination regimen that did not contain thalidomide or
vincristine or refractory defined as progressed while receiving that
anti-myeloma tx

- In between the IV bort.-based combination regimen and this study, the pt may
have received other non-bort.-based regimens as long as these treatments did not
contain thalidomide or vincristine

4. Voluntary written informed consent before performance of any study-related procedure
not part of normal medical care

5. Age: ≥18 yrs at the time of consent

6. Able to adhere to the study visit schedule and other protocol requirements

7. ECOG performance status of ≤ 2 at study entry

8. Life-expectancy > 3 mos

9. Laboratory test results w/in these ranges at Screening and confirmed at enrollment
prior to drug dosing on Cycle 1, Day 1:

- ANC ≥ 1.5 x 109/L; if the bone marrow is extensively infiltrated (> 70% plasma
cells) then ≥ 1.0 x 109/L

- Platelet count ≥ 75 x 109/L; if the bone marrow is extensively infiltrated (>
70% plasma cells) then ≥ 50 x 109/L

- Hgb > 8 g/dL

- Calculated or measured CrCl of at least 30 mL/min. (see protocol)

- Total Bili ≥ 1.5 x ULN

- AST (SGOT) and ALT (SGPT) ≥ 3 x ULN ≥ 5 x ULN if hepatic metastases are present

- Serum potassium WNL

10. Female pt is either postmenopausal for 1 year or greater before the screening visit,
is surgically sterilized or if they are of childbearing potential, agree to practice
2 effective methods of contraception from the time of signing the informed consent
form through 30 days after the last dose of VELCADE, or agree to completely abstain
from heterosexual intercourse.

11. Male patients who agree to 1) practice effective barrier contraception during the
entire study treatment period and through a minimum of 30 days after the last dose of
study drug, or 2) completely abstain from heterosexual intercourse.

Exclusion Criteria:

1. POEMS syndrome

2. PCL

3. Primary amyloidosis

4. Diagnosed or treated for another malignancy w/in 3 yrs 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.

5. ≤ Grade 2 peripheral neuropathy

6. Pt had myocardial infarction w/in 6 months prior to enrollment or has NYHA Class III
or IV heart failure, uncontrolled angina, severe uncontrolled ventricular
arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction
system abnormalities.

7. Severe hypercalcemia, i.e., serum calcium ≤ 12 mg/dL (3.0 mmol/L) corrected for
albumin

8. Undergone major surgery w/in 28 days prior enrollment or has not recovered from side
effects of such therapy (see protocol)

9. Received the following prior therapy:

- Thalidomide or vincristine alone or as part of a treatment regimen administered
between the last IV bort.-based regimen and Cycle 1, Day 1 on this study.
However, prior exposure to thalidomide or vincristine is allowed.

- Chemotherapy w/in 21 days of study drugs (6 weeks for nitrosoureas)

- Corticosteroids (>10 mg/day prednisone or equivalent) w/in 21 days of study
drugs unless steroids are being administered at that dose or greater as part of
the new regimen

- Immunotherapy or antibody therapy as well as lenalidomide, arsenic trioxide or
bort. w/in 21 days before study drugs

- Radiation therapy w/in 21 days before study drugs. (see protocol for exceptions)

- Use of any other experimental drug or therapy w/in 28 days of study drugs

10. Participation in clinical trials with other investigational agents not included in
this trial, w/in 14 days of the start of this trial and throughout the duration of
this trial.

11. Hypersensitivity to VELCADE (bort.), boron, or mannitol.

12. Concurrent use of other anti-cancer agents or treatments

13. Pregnant or lactating patients

14. Serious medical or psychiatric illness

15. Known positivity for HIV or hepatitis B or C