Phase II Trial of Ofatumumab and Bortezomib in Subjects With Relapsed CD20+ Diffuse Large B Cell Lymphoma, Follicular Lymphoma, or Mantle Cell Lymphoma

Inclusion Criteria:

- Patients must have biopsy sample obtained within 6 months of study entry that:

- Is histologically confirmed DLBCL, MCL or FL, by an Oregon Health and Science
University (OHSU) hematopathologist

- Retains expression of CD20+

- Patients must be refractory to or have recurrent disease after prior rituximab
containing treatment; relapse or progression is defined according the International
Working Group (IWG) response criteria

- FL patients must have disease-related symptoms, cytopenias, threatened end-organ
function, bulky or progressive disease, or it is the patient's preference to be
treated

- DLBCL and MCL patients must be either transplant ineligible or have refused high dose
therapy

- Patients must have radiographically measurable disease, as defined by the IWG
criteria; the same method of assessment used to measure each lesion at baseline must
be used for all subsequent tumor measurements throughout the study

- There is no limit to the number of prior treatments

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Absolute neutrophil count >= 1.0 K/mm^3

- Platelets >= 50 K /mm^3

- Total bilirubin =< 1.5 x normal institutional limits, unless secondary to Gilbert's
disease

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
=< 2.5 x institutional upper limit of normal (ULN)

- Alkaline Phosphatase < 2.5 times ULN (unless due to disease involvement of the liver
or bone marrow)

- Patients must be able to comply with study procedures and follow-up examinations

- Women of childbearing potential (not surgically sterile or < 12 months naturally
post-menopausal) must be willing to use medically accepted method of contraception
for the duration and 6 months following the end of the treatment; acceptable methods
of contraception include abstinence, barrier method with spermicidal or hormonal
contraceptive (oral, transdermal, implanted and injected) in conjunction with a
barrier method

- Men who are not surgically sterile must practice abstinence or use a barrier method
of birth control for the duration and 6 months following the end of treatment

- Patients must have the ability to understand and the willingness to sign a written
informed consent document

Exclusion Criteria:

- Subjects who have current active hepatic or biliary disease (with the exception of
patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable
chronic liver disease per investigator assessment)

- Patients who have had chemotherapy, antibody or radiotherapy within 4 weeks (6 weeks
for nitrosoureas or mitomycin C); corticosteroids for symptom control are allowed up
to 7 days of starting protocol treatment

- Patients may not have received any other investigational agents within 4 weeks, or
may not be currently participating in any other interventional clinical study

- Prior treatment with ofatumumab or bortezomib

- Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 3 months
prior to start of therapy

- Diagnosis of another malignancy, unless the patient has been disease-free or at least
5 years following the completion of curative intent therapy with the following
exceptions: patients with treated non-melanoma skin cancer, in situ carcinoma, or
cervical intraepithelial neoplasia, regardless of the disease-free duration, are
eligible for this study if definitive treatment for the condition has been completed;
patients with organ-confined prostate cancer with no evidence of recurrent or
progressive disease based on prostate-specific antigen (PSA) values are also eligible
for this study if hormonal therapy has been initiated or a radical prostatectomy has
been performed

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to ofatumumab or bortezomib

- Peripheral neuropathy or neuropathic pain of Grade 2 or greater

- Chronic or current infectious disease requiring systemic antibiotics, antifungal, or
anti-viral treatment such as, but not limited to, chronic renal infection, chronic
chest infection with bronchiectasis and tuberculosis

- History of significant cerebrovascular disease in the past 6 months or ongoing event
with active symptoms or sequelae

- Clinically significant cardiac disease including unstable angina, acute myocardial
infarction within six months prior to randomization, congestive heart failure (New
York Heart Association [NYHA] III-IV), and arrhythmia unless controlled by therapy,
with the exception of extra systoles or minor conduction abnormalities

- Significant concurrent, uncontrolled medical condition including, but not limited to,
renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or
psychiatric disease which in the opinion of the investigator may represent a risk for
the patient

- Pregnant or breast feeding women

- Known human immunodeficiency virus (HIV) infection

- Positive serology for Hepatitis B (HB) defined as a positive test for HB surface
antigen (HBsAg); in addition, if negative for HBsAG but HB core antibody (HBcAb)
positive (regardless of HBsAb status), a HB deoxyribonucleic acid (DNA) test will be
performed; if positive the subject will be excluded

- Active hepatitis C infection (HC) defined as a positive test for HCAb, in which case
the investigator should reflexively perform a HC Recombinant Immunoblot assay (RIBA)
on the same sample to confirm the result

- Known lymphoma involvement of the central nervous system (CNS)