Lymphoma
Conditions
Keywords
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
Brief summary
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
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.
Interventions
DRUGchlorambucil
DRUGfludarabine phosphate
PROCEDUREquality-of-life assessment
Sponsors
Taunton and Somerset Hospital
Study design
Allocation
RANDOMIZED
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Response to therapy (complete and partial response rates) | — |
| Duration of response | — |
Secondary
| Measure | 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 | — |
Countries
Australia, United Kingdom
Outcome results
None listed