Chlorambucil or Fludarabine as First-Line Therapy in Treating Patients With Previously Untreated Waldenström Macroglobulinemia, Splenic Lymphoma, or Lymphoplasmacytic Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as chlorambucil and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known whether chlorambucil is more effective than fludarabine in treating Waldenström macroglobulinemia, splenic lymphoma, or lymphoplasmacytic lymphoma. PURPOSE: This randomized phase III trial is studying chlorambucil to see how well it works compared with fludarabine as first-line therapy in treating patients with previously untreated Waldenström macroglobulinemia, splenic lymphoma, or lymphoplasmacytic lymphoma.

Detailed Description
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OBJECTIVES: Compare the efficacy of first-line therapy comprising chlorambucil vs fludarabine phosphate in patients with previously untreated Waldenström macroglobulinemia, splenic lymphoma with villous lymphocytes, or non-IgM lymphoplasmacytic lymphoma. OUTLINE: This is a multicenter study. Patients are stratified according to disease (Waldenström macroglobulinemia vs splenic lymphoma with villous lymphocytes vs non-IgM lymphoplasmacytic lymphoma). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral chlorambucil on days 1-10. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive fludarabine phosphate orally or IV on days 1-5. Treatment repeats every 28 days for 3-6 courses in the absence of disease progression or unacceptable toxicity. Patients undergo quality of life assessment at baseline.

Official Title
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A Randomised Trial of Chlorambucil Versus Fludarabine as Initial Therapy of Waldenström's Macroglobulinaemia and Splenic Lymphoma With Villous Lymphocytes

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: chlorambucil
* Drug: fludarabine phosphate
* Procedure: quality-of-life assessment


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of Waldenström macroglobulinemia, splenic lymphoma with villous lymphocytes (SLVL), or non-IgM lymphoplasmacytic lymphoma based on morphological and immunophenotypic criteria Bone marrow should be assessed by two-color flow cytometry for the expression of the following antigens: Surface Ig CD19 CD20 CD5 CD10 CD23 Previously untreated disease requiring therapeutic intervention (as judged by the primary physician), as indicated by ≥ 1 of the following: Hemoglobin < 10 g/dL ANC < 1.5 x 10^9/L Platelet count < 150 x 10^9/L Clinical evidence of hyperviscosity in terms of neurological or ocular disturbance Patients with disease detected by clonal cells alone are not eligible PATIENT CHARACTERISTICS: Performance status 0-2 Life expectancy > 6 months Serum creatinine < 200 mmol/L AST and ALT < 2 times upper limit of normal Negative direct Coomb's test Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy No severe or life-threatening cardiac, pulmonary, neurological, psychiatric, or metabolic disease No other concurrent malignancy No AIDS or AIDS-related complex No evidence of active hepatitis C infection PRIOR CONCURRENT THERAPY: Prior plasmapheresis for control of clinically significant hyperviscosity allowed Prior splenectomy for SLVL allowed

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
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: chlorambucil|nan|
|Drug: fludarabine phosphate|nan|
|Procedure: quality-of-life assessment|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to therapy (complete and partial response rates) |  |  | 
| Duration of response |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in hematological parameters |  |  | 
| Toxicity |  |  | 
| Quality of life as assessed by the European Organization for Research and Treatment of Cancer Quality of Life-30 questionnaire |  |  | 
| Survival |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Waldenström macroglobulinemia, splenic marginal zone lymphoma, stage I marginal zone lymphoma, stage III marginal zone lymphoma, stage IV marginal zone lymphoma, contiguous stage II marginal zone lymphoma, noncontiguous stage II marginal zone lymphoma