Inclusion Criteria:

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not part of normal medical care, with the understanding that consent may be withdrawn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

2. Female subject is either post-menopausal for at least 1 year 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. Male subjects, even if surgically sterilized
(ie, status postvasectomy) must agree to 1 of the following: 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 completely abstain from heterosexual
intercourse.

3. Diagnosis of multiple myeloma based on standard criteria as follows:

Major Criteria:

I. Plasmacytomas on tissue biopsy

II. Bone marrow plasmacytosis (>30% plasma cells)

III. Monoclonal immunoglobulin spike on serum electrophoresis (IgG >3.5 G/dL or IgA >
2.0 G/dL) or kappa or lambda light chain excretion> 1 G/day on 24 hour urine protein
electrophoresis

Minor Criteria

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

2. Monoclonal immunoglobulin present but of lesser magnitude than given under major
criteria

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 criteria will confirm the diagnosis of Multiple
Myeloma:

- Any two of the major criteria

- Major criterion I plus minor criterion b, c, or d

- Major criterion III plus minor criterion a or c

- Minor criteria a, b and c or a, b and d

4. Measurable disease, defined as a monoclonal immunoglobulin spike on serum
electrophoresis of ≥ 1 Gm/dL and/or urine monoclonal immunoglobulin spike of ≥ 200
mg/24 hours.

5. Patients must have refractory myeloma as defined by a greater than 25% increase in
their M-protein. They should have progressed on a combination of VELCADE and
cyclophosphamide.

6. Non-secretors must have measurable protein by Freelite or measurable disease such as
plasmacytoma to be eligible.

7. Karnofsky performance status ≥ 50

8. Patients treated with local radiotherapy with or without a brief exposure to steroids
are eligible. Patients who require concurrent radiotherapy should have entry to the
protocol deferred until the radiotherapy is completed

9. Meets the following pretreatment laboratory criteria at Baseline (Day 1 of Cycle 1,
before study drug administration)

- Absolute neutrophil count ≥ 0.5 x 10^3/uL

- Calculated or measured creatinine clearance ≥ 30 mL/min

10. Age 18 years or older

Exclusion Criteria:

1. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly,
endocrinopathy, monoclonal protein (M-protein) and skin changes)

2. Plasma cell leukemia

3. Receiving steroids daily for other medical conditions, e.g., asthma, systemic lupus
erythematosis, rheumatoid arthritis

4. Infection not controlled by antibiotics

5. HIV infection. Patients should provide consent for HIV testing according to the
institution's standard practice

6. Known active hepatitis B or C

7. Patient had myocardial infarction within 6 months prior to enrollment, New York
Hospital Association (NYHA) Class III or IV heart failure, (see appendix D),
uncontrolled angina, severe uncontrolled ventricular arrhythmias, or
electrocardiographic evidence of acute ischemia or active conduction system
abnormalities. Prior to study entry, any ECG abnormality at screening must be
documented by the investigator as not medically relevant.

8. Diagnosed or treated for another malignancy within 3 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.

9. Radiation therapy within 3 weeks before randomization. Enrollment of subjects who
require concurrent radiotherapy (which must be localized in its field size) should be
deferred until the radiotherapy is completed and 3 weeks have elapsed since the last
date of therapy.

10. Other serious medical or psychiatric illness that could potentially interfere with
the completion of treatment according to this protocol

11. Female subject is pregnant or lactating. Confirmation that the subject is not
pregnant must be established by a negative serum B-human chorionic gonadotropin (B
hCG) pregnancy test result obtained during screening. Pregnancy testing is not
required for postmenopausal or surgically sterilized women.

12. Patient has > Grade 2 peripheral neuropathy

13. Patient has known hypersensitivity to VELCADE, boron or mannitol, quinidine or
quinidine derivatives or to cyclophosphamide or any component of the formulation.

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

15. Patients with preexisting retinal or visual field changes.

16. Patient has > 1.5 x ULN Total Bilirubin