Bortezomib and Rituximab for Patients With Waldenstrom's Macroglobulinemia

Inclusion Criteria:

1. Patients with symptomatic macroglobulinemic lymphoma who have had no prior treatment, or whose prior treatment has been limited to steroids and/or alpha-interferon, are eligible. Macroglobulinemic lymphoma includes patients with either biopsy proven clonal lymphocytic or lymphoplasmacytic proliferation and monoclonal IgM. Also included are symptomatic patients with clonal proliferation producing a pathologic monoclonal IgM that causes cryoglobulinemia, peripheral neuropathy or cold agglutinin hemolytic anemia.
2. Patients must have acceptable liver function (total bilirubin \< 2.5mg/dL) and renal function (creatinine \< 2.0mg/dL). Patients with impaired renal function will only be included if the renal failure is secondary to macroglobulinemic lymphoma (i.e. Bence Jones proteinuria, cryoglobulinemia, ureteral obstruction due to mass) that might reverse with improvement of disease.
3. 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.
4. Male subject agrees to use an acceptable method for contraception for the duration of the study.
5. Patients must voluntarily sign an informed consent form indicating that they are aware of the investigational nature of the study, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future care.
6. Patient has a heart rate (HR) of greater than or equal to 50 bpm.

Exclusion Criteria:

1. Patient has a platelet count of \<30x10\^9/L within 28 days before enrollment unless due to \>/= 75% marrow infiltration by macroglobulinemic lymphoma or splenomegaly.
2. Patient has an absolute neutrophil count of \<1.0x10\^9/L within 28 days before enrollment unless due to \>/= 75% marrow infiltration by macroglobulinemic lymphoma.
3. Patient has a calculated or measured creatinine \>/= to 2.0mg/dL on baseline evaluation. Patients with impaired renal function will only be included if the renal failure is secondary to macroglobulinemic lymphoma (i.e. Bence Jones proteinuria, cryoglobulinemia, ureteral obstruction due to mass).
4. Patient has \>/= Grade 2 peripheral neuropathy on baseline evaluation.
5. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, 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.
6. Patient has hypersensitivity to boron, mannitol, or murine proteins.
7. Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum or urine Beta -human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
8. Patient has received other investigational drugs within 14 days before enrollment
9. Patient has a serious medical or psychiatric illness that is likely to interfere with participation in this clinical study.
10. Eastern Cooperative Oncology Group (ECOG) performance status of \> 2.
11. Patient with a "currently active" second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled. Patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for \> 5 years and are considered by their physician to be at less than 30 % risk of relapse.
12. Patient with a lifetime cumulative dose of \> 450 mg/m\^2 of anthracyclines.
13. Patients with an active hepatitis B infection.