Combination Bortezomib and Rituximab in Patients With Waldenstrom's Macroglobulinemia

• Evaluate the toxicity of VR in patients with WM [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]
• evaluate the time to progression in patients with WM [ Time Frame: Years ] [ Designated as safety issue: No ]
• Study the effect of bortezomib and rituximab on tumor cells in this patient population. [ Time Frame: 2 Years ] [ Designated as safety issue: No ]

• Evaluate the toxicity of VR in patients with WM
• evaluate the time to progression in patients with WM
• Study the effect of bortezomib and rituximab on tumor cells in this patient population.

• Participants will receive 6 cycles of the study treatment with bortezomib and rituximab. Each cycle is 28 days long (4 weeks).
• Participants will receive Rituximab intravenously once a week for the first and fourth cycles only. Participants will receive bortezomib once a week for three weeks on and one week off every cycle, for a total of 6 cycles.
• During the rituximab infusion, the participants blood pressure and pulse will be monitored frequently. The rate of infusion may be decreased depending upon the side effects that are experienced.
• Blood samples will be collected before the first dose and on follow up with every cycle. Blood counts will also be performed every week.
• Routine physical exams will be performed at each evaluation. A PET/CAT scan of the chest, abdomen and pelvis at the end of treatment. This scan is required to assess the response of the participants disease.
• In order to learn more on how bortezomib and rituximab affect WM, a bone marrow biopsy will be performed.
• We anticipate that participants will complete the active therapy over a period of 6 cycles provided that they are benefiting from therapy and have not had any serious side effects. The participant will be followed every three months for 2 years for office visits and laboratory tests.

• Drug: Bortezomib
  Once weekly for 3 weeks
• Drug: Rituximab
  Intravenously once a week for the first and fourth weeks of a cycle

Inclusion Criteria:

• 18 years of age or older
• Patients with previously untreated WM and those who have received prior therapy are eligible
• Must have received prior therapy for their WM and have relapsed or refractory WM.
• CD20 positive disease based on any previous bone marrow immuno-histochemistry or flow cytometric analysis performed up to 3 months prior to enrollment.
• Measurable disease
• ECOG Performance Status 0,1, or 2
• Total bilirubin < 2.0 mg/dl
• AST < 3 x ULN
• Life expectancy of greater than 12 weeks

Exclusion Criteria:

• Uncontrolled infection
• Other active malignancies
• Cytotoxic chemotherapy less than 3 weeks, or biologic therapy less than 2 weeks, or corticosteroids less than 2 weeks, prior to registration.
• Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational
• Known to be HIV positive or HEP B positive
• Radiation therapy less than 2 weeks prior to registration
• Grade 2 or greater peripheral neuropathy
• Myocardial infarction within 6 months rior to enrollment or has NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Hypersensitivity to bortezomib, boron, or mannitol
• Pregnant or breast feeding women
• Other investigational drugs within 14 days of enrollment
• Serious medical or psychiatric illness likely to interfere with participation