Thalidomide and Rituximab in Waldenstrom's Macroglobulinemia

Study Overview
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Brief Summary
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The purpose of this study is to determine the percentage of people who can attain remission and the length of time such responses to therapy are sustained, as well as the side effects that might result from rituximab and thalidomide in people with lymphoplasmacytic lymphoma.

Detailed Description
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Patients will receive thalidomide(200mg) orally once daily for two weeks. If after two weeks of thalidomide, the patient is doing well the dose of thalidomide will increase (400mg) and they will remain on it for up to 50 additional weeks. The length of time a patient is on thalidomide will depend upon how they are responding to therapy. During the second week of the study patients will also begin receiving rituximab intravenously once weekly for 4 weeks, which may then be repeated 8 weeks later depending upon the response. A determination of how the patient is responding will be made based on testing conducted at 12 weeks. This testing includes blood tests and possibly a bone marrow biopsy. If it is determined that the disease is not progressing, patients will begin a second phase of treatment which includes 4 additional weekly infusions of rituximab and the continuation of oral thalidomide. If it is determined at the 12-week evaluation, or at any time thereafter, that the disease has progressed (by studying serum immunoglobulin M (IgM) levels, bone marrow involvement, tumor cells, and/or development of new signs and symptoms) then the patient will be removed from the study. Periodic examinations and tests will be done to determine how the patient is doing, what response and side effects (if any) the patient may be having from the study drugs. If patient is responding to therapy then they will remain on this study and followed for a period of two years. Bone marrow biopsies and aspirations will be obtained at 3-6 month intervals extending for 2 years following the last treatment.

Official Title
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Phase II Study of Thalidomide and Rituximab in Waldenstrom's Macroglobulinemia

Conditions
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Waldenstrom's Macroglobulinemia, Lymphoplasmacytic Lymphoma

Intervention / Treatment
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* Drug: Thalidomide
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinicopathological diagnosis of Waldenstrom's macroglobulinemia requiring therapy Baseline staging requirements Absolute Neutrophil Count > 500/microliter (uL) Platelet Count > 25,000/uL Serum creatinine < 2.5mg/dL Total bilirubin and transaminase (SGOT) < 2.5 X Upper Limit of Normal (ULN) Greater than 18 years of age Life expectancy of 3 months or greater Eastern Cooperative Oncology Group (ECOG) status performance of 0-2 Exclusion Criteria: Chemotherapy, steroid therapy, or radiation therapy within 30 days of study entry Pregnant or lactating women Serious co-morbid disease Uncontrolled bacterial, fungal or viral infection Active second malignancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Thalidomide and Rituximab<br>Thalidomide 200mg orally once a day for 14 weeks if that dosage is tolerated well, it will be increased to 400mg for up to 50 weeks Rituximab Given intravenously once weekly for 4 weeks beginning the second week of study treatment. If tolerated well, this may be repeated 8 weeks later. | Drug: Thalidomide<br>* 200mg orally once a day for 14 weeks if that dosage is tolerated well, it will be increased to 400mg for up to 50 weeks.<br>* Other names: Thalomid;Drug: Rituximab<br>* Given intravenously once weekly for 4 weeks beginning the second week of study treatment. If tolerated well, this may be repeated 8 weeks later.<br>* Other names: Rituxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Response determinations were made using modified consensus panel criteria from the Third International Workshop on WM, and response rates were determined on an evaluable basis. A complete response was defined as having resolution of all symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, and resolution of any adenopathy or splenomegaly. Patients achieving a partial response and a minor response were defined as achieving a more than or equal to 50% and more than or equal to 25% reduction in serum IgM levels, respectively. Patients with stable disease were defined as having less than 25% change in serum IgM levels, in the absence of new or increasing adenopathy or splenomegaly and/or other progressive signs or symptoms of WM. Progressive disease was defined as a greater than 25% increase in serum IgM level occurred from the lowest attained response value or progression of clinically significant disease-related symptom(s). | 3 years | 
| Time to Progression | Time to disease progression (TTP) was calculated from the start of therapy using the Kaplan-Meier method. | 49.1 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Identify the Mechanism(s) of Action for Combined Thalidomide and Rituximab Activity. |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thalidomide, rituximab, Waldenstrom's