VELCADE®-BEAM and Autologous Hematopoietic Stem Cell Transplantation for Non-Hodgkin's Lymphoma, or Mantle Cell Lymphoma

Primary Objective:The primary objective of the study is to evaluate the toxicity and
determine the maximum tolerated dose (MTD) of bortezomib when added to a standard BEAM
(carmustine (BCNU), etoposide, cytarabine, melphalan) conditioning regimen followed by
autologous hematopoietic stem cell transplantation (ASCT).

Secondary Objective: The secondary objective of the study is to obtain a preliminary estimate
of the overall response rate (ORR), progression free survival (PFS), and overall survival
(OS) with this regimen.

Enrolled subjects will receive bortezomib in combination with BEAM (carmustine (BCNU),
etoposide, cytarabine, melphalan) and autologous hematopoietic stem cell transplantation
(AHSCT). Phase I treatment will administer bortezomib in four dose cohorts,in addition to the
BEAM and ASCT. Three patients will be accrued in each dose cohort with enrollment starting at
dose cohort. These subjects will be evaluated to establish the maximum tolerated dose of
bortezomib in combination with BEAM autologous peripheral blood stem cell transplantation.
Once established, the maximum tolerated dose will be utilized in treating an additional 20
subjects.

Follow-Up: Data collected will be utilized to obtain a preliminary estimate of the overall
response rate, progressions free survival and overall survival using this regimen.

Inclusion Criteria:

- Persistent, relapsed or refractory indolent non-Hodgkin's lymphoma (Follicular grade
I, II, or III), non-Hodgkin's lymphoma, composite lymphomas with ≥ 50% of tumor
showing follicular histology, transformed follicular, lymphoplasmacytic, marginal zone
lymphoma, small Lymphocytic Lymphoma (including T-cell subtypes), or mantle cell
lymphoma that is relapsed, refractory, or in PR1 or CR1 (MCL only for CR1).

- Age >19 years.

- Signed written informed consent.

- Expected survival duration of > six months.

- Karnofsky Performance Status > 70.

- Eligible patients must have: Liver functions < 3x upper limits of normal (ULN) unless
due to disease; ANC > 500 cells/mm3 and Platelet Count > 50 mm3.

- Patients > age 60 or with clinical signs of heart disease must have ejection fraction
≥ 45% LVEF.

- Patients with clinical signs of pulmonary insufficiency must have DLCO to be measured
at > 50% of predicted value.

- Able to collect > 1.2 X 106/kg CD34+ cell for transplantation.

- No serious disease or condition that, in the opinion of the investigator, would
compromise the patient's ability to participate in the study.

- Female patients must not be pregnant or lactating.

- Male and female patients of reproductive potential must follow accepted birth control
measures.

Exclusion Criteria:

- Patients who are HIV seropositive

- Serum creatinine >2.5mg/dL or calculated creatinine clearance ≤ 50ml/min

- Total bilirubin >3 times upper limits of normal (unless due to Gilberts disease or
malignancy), ALT and AST >4 times the upper limits of normal

- Active infection at the time of transplant

- Myocardial infarction within 6 months prior to enrollment or has New York Hospital
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 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 pregnancy test result obtained during
screening. Pregnancy testing is not required for post-menopausal or surgically
sterilized women.