Study closed by PI due to lower than expected accrual.

This phase II trial studies how well giving ofatumumab together with bortezomib works in treating patients with relapsed diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), or mantle cell lymphoma (MCL). Monoclonal antibodies, such as ofatumumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving ofatumumab together with bortezomib may help kill more cancer cells

PRIMARY OBJECTIVES:

I. To determine the efficacy, as measured by overall response (complete response (CR) + partial response (PR)) of ofatumumab in combination with bortezomib in subjects with relapsed cluster of differentiation (CD)20+ DLBCL, FL or MCL.

SECONDARY OBJECTIVES:

I. To explore duration of efficacy of ofatumumab in combination with bortezomib in the same population as measured by progression free survival (PFS), overall survival (OS) and disease free survival (DFS).

II. To assess response as compared to prior treatment. III. To assess the safety and tolerability of ofatumumab in combination with bortezomib in the same patient population.

TERTIARY OBJECTIVES:

I. Correlation of trough ofatumumab blood levels to response. II. Correlation fragment crystallizable receptor (FcR) gamma 3 allotype and response.

OUTLINE:

Patients receive ofatumumab intravenously (IV) over 2.5 hours on days 1 and 8 of course 1, and day 1 of all subsequent courses. Patients also receive bortezomib IV over 3-5 seconds on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment patients are followed up every 3 months for 2 years.

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 hepatitis C antibody (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)