Inclusion Criteria:

• Tissue diagnosis of a previously untreated, CD20+, B-Cell Non-Hodgkin Lymphoma.
• For the Phase 1 trial: Patients with any of the following diagnoses are eligible:
• Follicular Lymphomas (Grade 1, 2, 3a, 3b)
• Small Lymphocytic Lymphoma
• Marginal Zone Lymphomas
• For the Phase 2 trial: Patients with any of the following diagnoses are eligible:
• Follicular Lymphomas (Grade 1, 2, 3a)
• Small Lymphocytic Lymphoma
• Marginal Zone Lymphomas

• Patients with follicular or other low-grade lymphoma must have an indication for treatment based on modified GELF criteria or a FLIPI score

  • 3
• Indications for treatment based on modified GELF criteria include any one of the following:
• B symptoms or other lymphoma-related symptoms
• Involvement of 3 nodal sites, each with a diameter of 3 cm
• Any nodal or extranodal tumor mass with a diameter of 7 cm
• Splenomegaly
• Pleural effusions or peritoneal ascites
• Cytopenias (leukocytes < 1.0 x 10 /L and/or platelets < 100 x 10 /L)
• Leukemia (> 5.0 x 10 /L circulating malignant cells)
• Indications for treatment based on FLIPI criteria include any three of the following:
• Age ≥60 years
• Ann Arbor stage III or IV
• Hemoglobin level <120 g/L
• Number of nodal areas involved >4
• Serum LDH level >normal
• Only chemotherapy-naïve subjects are eligible. Subjects may have received prednisone (< 2 months of therapy) or radiation ≤ 2 sites of therapy.
• Voluntary written informed consent and HIPAA Authorization 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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.
• Female patients of child bearing potential must have a negative beta-HCG test.
• Male subject agrees to use an acceptable method for contraception for the duration of the study.
• ≥18 years of age at the time of registration
• Patients must have adequate renal function as demonstrated by a serum creatinine < 1.5 mg/dl unless felt to be secondary to lymphoma
• Must have an ALT/AST ≤ 3.5 the upper limit of normal and a total bilirubin ≤2.0 mg/dL unless secondary to lymphoma.
• Must have a cardiac left ventricular ejection fraction ≥50%.
• At least 1 measurable tumor mass (greater than 1.5 cm in the longest dimension and greater than 1.0 cm in the short axis)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Life expectancy of greater than one year.

Exclusion Criteria:

• Subject with primary or secondary CNS lymphoma (current or previously treated) will not be eligible.
• A history of unrelated (non-lymphomatous) neoplasm within the past 10 years other than non-melanoma skin cancer or in-situ cervix cancer. Subjects with a prior diagnosis of malignancy more than 10 years may be entered into the study at the discretion of the Principal Investigator.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Patient has received other investigational drugs with 14 days before enrollment.
• Patient has hypersensitivity to boron or mannitol.
• Female subject is pregnant or breast-feeding. Chemotherapeutic agents are known to have teratogenic effects on developing embryos and to cause chromosomal damage to gametes. These agents also cause bone marrow suppression and can be excreted in milk. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG)pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• 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 a platelet count of < 10 x 1010/L (unless due to bone marrow involvement with lymphoma documented within 14 days before enrollment).
• Patient has an absolute neutrophil count of <1.0 x 109/L (unless due to bone marrow involvement with lymphoma documented within 14 days before enrollment).
• Patient has a calculated or measured creatinine clearance of <20 mL/minute within 14 days before enrollment.
• Presence of antibodies to HIV.
• Subject unwilling to give informed consent.
• Failure to meet any of the eligibility criteria in Section 3.2.1.