Phase I Study of Bortezomib With G-CSF for Stem Cell Mobilization in Patients With Multiple Myeloma

The purpose of this phase I study is to define the maximum tolerated dose of bortezomib and
its mobilization effects when given with G-CSF for stem cell mobilization in multiple myeloma
patients. We hypothesize that bortezomib, in addition to increasing the number of mobilized
stem cells, will optimize final apheresis product by decreasing myeloma cell contamination.
Therefore, all multiple myeloma patients rather than multiple myeloma patients with G-CSF
mobilization failure will be the target of this study.

Inclusion Criteria:

- Histologically confirmed diagnosis of multiple myeloma.

- Eligible for autologous transplantation.

- Received at least two cycles of any regimen as initial systemic therapy for multiple
myeloma and are within 2-12 months of the first dose of initial therapy.

- At least 18 years of age.

- ECOG performance status ≤ 2

- Normal bone marrow and organ function as defined below:

- Platelets ≥ 50,000/mm3

- Hemoglobin ≥ 8.0 g/dL

- Absolute neutrophil count ≥1,000/mm3

- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN

- Total bilirubin ≤ 1.5 x IULN

- Measured or calculated creatinine clearance ≥ 30 mL/min

- Female patients who:

- are postmenopausal for at least 1 year before the screening visit OR

- are surgically sterile OR

- Women of childbearing potential and men must agree to practice 2 effective
methods of contraception prior to study entry, for the duration of study
participation, and for 30 days after the last dose of study treatment. Should a
woman become pregnant or suspect she is pregnant while participating in this
study, she must inform her treating physician immediately.

- Ability to understand and willingness to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

- Previous stem cell collection or transplantation (autologous or allogeneic).

- Evidence of multiple myeloma disease progression (as defined by IMWG) any time prior
to auto-HSCT.

- Diagnosis of plasma cell leukemia.

- Concurrent hematologic or non-hematologic malignancy requiring treatment (other than
multiple myeloma or secondary amyloidosis).

- Radiation therapy within 3 weeks prior to enrollment.

- Grade 2 or higher peripheral neuropathy.

- Known hypersensitivity to any of the following: bortezomib, boron, mannitol.

- Myocardial infarction within 6 months prior to enrollment or New York Heart
Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
ischemia or active conduction system abnormalities

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, or serious medical or psychiatric
illness/social situations that would limit compliance with study requirements.

- Female patients who are pregnant and/or breastfeeding. Patient must have a negative
serum pregnancy test within 14 days of study entry.

- Known HIV-positivity. These patients are at increased risk of lethal infections when
treated with marrow-suppressive therapy. Appropriate studies will be undertaken in
patients with HIV-positivity when indicated.

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