Ofatumumab and Bortezomib for Patients With Low-grade B-cell Non-hodgkin Lymphoma That Relapse After Rituximab

Inclusion Criteria:

* Patients are required to have histologically confirmed lymphoma according to the WHO/Revised European-American Lymphoma classification, including B-cell small lymphocytic lymphoma (SLL); marginal zone lymphoma (MZL); follicular lymphoma (FL), grades 1, 2, or 3; mantle cell lymphoma (MCL); and Waldenström macroglobulinemia. Prior history of transformed lymphoma is permitted as long as recent biopsies revealed no evidence of aggressive lymphoma and it has been \> 3years since prior aggressive lymphoma
* Patients must measurable disease (defined as 1 cm with spiral computed tomography scan)
* Relapse of disease beyond 6 months after rituximab-containing regimen
* Patients had to have received no more than three prior lines of conventional cytotoxic therapy, and were required to have stopped receiving cytotoxic chemotherapy for at least 4 weeks before study enrollment
* Absolute neutrophil count \> 1,500/uL and Platelet \> 100,000/uL (if known lymphomatous involvement of the bone marrow, then absolute neutrophil count \> 750/uL and platelet count of \> 50,000/uL) within 14 days of enrollment.
* Total bilirubin \< 1.5 x upper institutional limit of normal (ULN), and AST or ALT \< 2.5 x ULN (\< 3 x ULN if the patient had liver involvement); alkaline phosphatase \< 2.5x upper limit of normal; and a creatinine \< 2mg/dl within 14 days of enrollment.
* ECOG performance status 0 to 2
* Minimum life expectancy of 6 months
* Age older than 18 years
* Voluntary, signed written informed consent 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
* Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
* Male subject agrees to use an acceptable method for contraception for the duration of the study.

Exclusion Criteria:

* Subjects who have current active hepatic or biliary disease asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
* Documented infection with HIV
* Positive serology for Hepatitis B defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded.
* Central nervous system or meningeal involvement by lymphoma
* Prior transplantation
* Contraindication to any drug contained in the chemotherapy regimens
* Any serious active disease or co-morbid condition that would impair protocol treatment.
* Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal call carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
* Prior treatment with any anti-CD20 monoclonal antibody, with the exception of rituximab, or any proteasome inhibitor.
* 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 (see section 8.4), 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 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. A pregnancy test must be performed within 7 days prior to study drug. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
* Patient has received other investigational drugs within 4 weeks before enrollment or 5 half lives of the investigational agent.
* Serious medical or psychiatric illness likely to interfere with participation in this clinical study.