Combination Bortezomib and Rituximab in Patients With Waldenstrom's Macroglobulinemia (WM)

Study Overview
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Brief Summary
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In this study, we are trying to find out if the combination of these two drugs is effective in treating Waldenstrom's macroglobulinemia (WM). The combination of these two drugs has not been studied for patients with relapsed or refractory macroglobulinemia. The U.S. Food and Drug Administration (FDA) has approved bortezomib for the treatment of multiple myeloma, a cancer that is closely related to Waldenstrom's macroglobulinemia.

Detailed Description
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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.

Official Title
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Phase II Study of Combination Bortezomib (Velcade PS-341) and Rituximab in Patients With Previously Untreated and Relapsed/Refractory Waldenstrom's Macroglobulinemia

Conditions
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Waldenstrom's Macroglobulinemia

Intervention / Treatment
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* Drug: Bortezomib
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bortezomib and rituximab<br>bortezomib and rituximab | Drug: Bortezomib<br>* Once weekly for 3 weeks<br>* Other names: Velcade;Drug: Rituximab<br>* Intravenously once a week for the first and fourth weeks of a cycle<br>* Other names: Rituxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate of Bortezomib and Rituximab (VR) in Patients With Relapsed or Refractory Waldenstrom's Macroglobulinemia (WM) | Overall Response Rate= Minor response (>25%-50% reduction in monoclonal IgM from baseline + Partial Response (>50-90% reduction in monoclonal IgM from baseline)+ Complete Response (Disappearance of monoclonal protein by immunofixation; no histologic evidence of bone marrow involvement, resolution of any adenopathy/organomegaly (confirmed by CT scan), or signs or symptoms attributable to WM. Reconfirmation of the CR status is required at least 6 weeks apart with a second immunofixation.) | 2 Years | 
| Overall Response Rate of Bortezomib and Rituximab (VR) in Patients With Previously Untreated Waldenstrom's Macroglobulinemia (WM) | Overall Response Rate= Minor response (>25%-50% reduction in monoclonal IgM from baseline + Partial Response (>50-90% reduction in monoclonal IgM from baseline)+ Complete Response (Disappearance of monoclonal protein by immunofixation; no histologic evidence of bone marrow involvement, resolution of any adenopathy/organomegaly (confirmed by CT scan), or signs or symptoms attributable to WM. Reconfirmation of the CR status is required at least 6 weeks apart with a second immunofixation.) | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression in Patients With WM | Time to progresion is the defined as the time from study entry to disease progression (PD) or death. Patients without PD are censored at the date of last disease evaluation. PD is defined as a greater than 25% increase in serum monoclonal IgM electrophoresis confirmed by a second measurement at least 2 weeks apart, or progression of clinically significant findings due to disease or symptoms attributable to WM. | 5 Years | 
| Duration of Response in Patients With WM | Time from documentation of first response to progressive disease. | 5 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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relapsed Waldenstrom's macroglobulinemia, refractory Waldenstrom's macroglobulinemia, Velcade, WM