Rituximab, Cyclophosphamide, Bortezomib, and Prednisone in Patients With Stage III/IV FL or MZL

Inclusion Criteria

* Voluntary 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
* Histologically confirmed, untreated follicular lymphoma (FL) grade I, II or marginal zone lymphoma (MZL) Stage III or IV
* Presence of measurable or evaluable disease
* Age \>17 years old
* Patients must have normal organ and marrow function as defined below, within 14 days of enrollment:

  * Serum bilirubin \< 2.0 mg/dL
  * serum creatinine \< 2 mg/dL unless due to lymphoma
  * Absolute Neutrophil Count (ANC) \>1000/mm3
  * Platelets \>100,000/mm3 unless due to lymphoma
  * Aspartate Transaminase (AST), Alanine Aminotransferase (ALT) and Alkaline phosphatase \< 3x the upper limit of normal
* Eastern Cooperative Oncology Group (ECOG) performance status of 1, 2, 3
* No prior therapy for the FL or MZL including chemotherapy, single agent rituximab and radiation therapy
* 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

* 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 Appendix 5), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
* 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 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 received other investigational drugs with 14 days before enrollment
* Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
* History of HIV infection (testing not required)
* Concurrent or previous malignancy whose prognosis is poor (\< 90% probability of survival at 5 years) or those who are actively being treated for a second malignancy.