A Dose Escalation of Zarnestra (R115777) Combined With Velcade® (PS-341) in Patients With Relapsed Multiple Myeloma

Inclusion Criteria:

- Voluntary written informed consent

- Female subject is either post-menopausal/surgically sterilized or willing to use an
acceptable method of birth control for the duration of the study.

- Male subject agrees to use an acceptable method for contraception for the duration of
the study.

- Diagnosis of stage II or III multiple myeloma and have relapsed after at least one
prior therapies confirmed by the presence of:

1. A new lytic lesion

2. A 25% increase in urine or serum monoclonal protein

- Patient can have received PS-341 (Velcade) previously and does not require a previous
response.

- Patients must have measurable disease. One or more of the following must be present
to qualify for this study:

1. Serum M-component greater than or equal to 1.0 gm/dl (10.0 g/L) by serum protein
electrophoresis

2. Urine M-protein excretion > 200 mg/24 (0.2 g/24h) hours, by urine protein
electrophoresis

3. Abnormal serum free light chain ratio with elevated Kappa or Lambda light chains
in serum

- Baseline measurements must be done within 21 days of study entry.

- Karnofsky Performance Status Scale > 60.

- Greater than or equal to 18 years of age.

- Expected survival of greater than 8 weeks.

- Swallow intact study medication tablets.

- Can follow directions or has a caregiver who will be responsible for administering
study medication.

Exclusion Criteria:

- Previously treated with R115777 (Zarnestra).

- Undergone an allogeneic bone marrow transplant.

- A platelet count of <100,000 x 10 to the 9 power/L within 14 days before enrollment.

- Absolute neutrophil count of <1.0 x 10 to the 9 power/L within 14 days before
enrollment.

- Measured creatinine > 1.5 X the upper limits of normal within 14 days before
enrollment.

- Greater than or equal to Grade 2 peripheral neuropathy within 14 days before
enrollment.

- Hypersensitivity to bortezomib, boron, mannitol or imidazole compounds

- Female subject is pregnant or breast-feeding. Confirmation that the subject is not
pregnant must be established by a negative serum beta-human chorionic gonadotropin
(beta-hCG) pregnancy test result obtained during screening.

- Received other investigational drugs within 14 days of enrollment or immunotherapy
within 30 days of enrollment.

- Serious medical or psychiatric illness likely to interfere with participation in this
clinical study.

- Ongoing radiation therapy or radiation therapy within 14 days prior to first
treatment.

- Cytotoxic chemotherapy within 30 days prior to first treatment.

- Therapy with high-dose corticosteroids within 14 days prior to first treatment.

- Presence of any of the following excludes a patient from entering the study until
such condition is resolved (determined within 14 days prior to the first treatment):

1. Elevated total bilirubin > 2mg/dl, or direct bilirubin > 2 times the ULN.

2. Serum glutamic oxaloacetic transaminase (AST, formerly SGOT) or serum glutamic
pyruvic transaminase (ALT, formerly SGPT) > 2 times the ULN

3. Serum calcium > 12 mg/dL.

4. Concurrent serious infection.

5. Life-threatening illness (unrelated to tumor).

- History of any other ACTIVE and INVASIVE cancer other than the present condition
(except non-melanoma skin cancer), unless in complete remission and off of all
therapy for that disease for a minimum of 3 years.

- Prohibited/allowable medications or precautions:

1. Enzyme-inducing anti-epileptic medications (e.g. phenytoin, phenobarbital,
carbamazepine) are not allowed.

2. Non-enzyme anti-epileptic medications will be allowed.