Bortezomib and Filgrastim in Promoting Stem Cell Mobilization in Patients With Non-Hodgkin Lymphoma or Multiple Myeloma Undergoing Stem Cell Transplant

PRIMARY OBJECTIVES:

I. To determine if addition of Bortezomib to the mobilization protocol will result with an
increase in the levels of circulating peripheral blood stem cells (PBSCs) by >= 2-fold in
blood and in the apheresis collections in up to 4-days collection protocol.

II. To achieve median neutrophil engraftment of 12 days.

SECONDARY OBJECTIVES:

I. To test for co-mobilization of lymphoma or myeloma cells by bortezomib and G-CSF using
real time polymerase chain reaction (PCR) for non-Hodgkin lymphoma (NHL) patients and by
flow cytometry (cluster of differentiation [CD]38+/CD138+ cell) for multiple myeloma (MM)
patients.

II. To determine the effect of Bortezomib on the extent of mobilization of dendritic cells
subsets, plasmacytoid dendritic cell (pDC)1 and pDC2 and DC1/DC2 ratio by flow cytometry.

OUTLINE: Patients are assigned to 1 of 2 treatment groups.

GROUP A: Patients receive filgrastim subcutaneously (SC) on days 1-9 and begin apheresis on
day 5. Patients undergo apheresis for up to 2 days, and receive bortezomib intravenously
(IV) over 3-5 seconds after target collection is obtained with filgrastim alone or on the
first day of collection with the Bortezomib plus filgrastim mobilization, prior to receiving
the administration of filgrastim. Second apheresis will continue until target stem cell dose
is reached or for maximum 4 days. Patients undergo autologous hematopoietic stem cell
transplantation after receiving high dose chemotherapy and peripheral blood stem cell (PBSC)
infusion following standard of care procedures.

GROUP B: Patients receive filgrastim SC on days 1-8 and receive bortezomib IV over 3-5
seconds on days 4 and day 7, before administration of filgrastim. Patients undergo apheresis
on days 5-8. Within 2 months after mobilization, patients undergo autologous hematopoietic
stem cell transplantation after receiving high dose chemotherapy and PBSC infusion as is the
standard of care.

After completion of study treatment, patients are followed at 1 month and 6 months.

Inclusion Criteria:

- Voluntary written informed consent form 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withdrawn by the subject at any time without prejudice to future medical care

- Diagnosis of B-type NHL or with multiple myeloma and eligible for autologous
transplantation

- No more than 3 prior regimens of chemotherapy (Rituximab is not considered
chemotherapy) and 4 weeks out of Bortezomib treatment for MM

- Karnofsky performance status of > 50%

- The patient has recovered from all acute toxic effects of prior chemotherapy

- White blood cell (WBC) > 3.0 x 10^9/L

- Absolute neutrophil count > 1.5 x 10^9/L

- Platelet count > 100 x 10^9/L

- Serum creatinine =< 2.2

- Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate
transaminase (SGPT) less than two times the upper limit of normal (ULN)

- Total bilirubin less than two times the ULN

- Left ventricle ejection fraction > 50% (by normal echocardiogram [ECHO] or multi
gated acquisition scan [MUGA] scan)

- Diffusing capacity of the lung for carbon monoxide (DLCO) > 50%

- Forced vital capacity > 50% of predicted

- Negative for human immunodeficiency virus (HIV)

- 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
use 2 effective methods of birth control (i.e., a hormonal contraceptive,
intra-uterine device, diaphragm with spermicide, condom with spermicide, or
abstinence) from the time of signing the informed consent form through 30 days after
the last dose of Bortezomib, or agree to completely abstain from heterosexual
intercourse; women of child bearing potential agree to use an approved form of
contraception; male subject, even if surgically sterilized (i.e., status
post-vasectomy) 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 for the duration of the study

Exclusion Criteria:

- Patient has a platelet count of < 100x 10^9/L within 14 days before enrollment

- Patient has an absolute neutrophil count of ANC <1.5 x 10^9/L within 14 days before
enrollment

- Patient has creatinine of > 2.2 MG/DL within 14 days before enrollment

- Patient has > 1.5 x ULN total bilirubin

- Patient has >= grade 2 peripheral neuropathy within 14 days before enrollment

- Myocardial infarction within 6 months prior to enrollment or has 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; prior to study entry, any
electrocardiogram (ECG) abnormality at screening has to be documented by the
investigator as not medically relevant

- Patient has hypersensitivity to Bortezomib, boron or mannitol

- 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
(b-hCG) pregnancy test result obtained during screening; pregnancy testing is not
required for post-menopausal or surgically sterilized women

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

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

- A co-morbid condition which, in the view of the investigators, renders the patient at
high risk for this study

- An acute medical condition resulting from prior chemotherapy

- Brain metastases or carcinomatous meningitis

- Acute infection

- Fever (temp > 38 degrees Celsius [C]/100.4 degrees Fahrenheit [F])

- Patients of child-bearing potential unwilling to implement adequate birth control

- Patients who have deterioration of their clinical status or laboratory parameters
between the time of enrollment and transplant (such that they no longer meet entry
criteria) may be removed from study at the discretion of the treating physician or
principal investigator

- 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

- 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