Rituximab and Combination Chemotherapy in Treating Patients With Newly Diagnosed Waldenstrom's Macroglobulinemia
Rituximab and Combination Chemotherapy in Treating Patients With Newly Diagnosed Waldenstrom's Macroglobulinemia
RATIONALE: Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill
 them or deliver cancer-killing substances to them without harming normal cells. Drugs used in
 chemotherapy work in different ways to stop cancer cells from dividing so they stop growing
 or die. Combining rituximab with combination chemotherapy may kill more cancer cells.

 PURPOSE: This phase II trial is studying how well giving rituximab together with combination
 chemotherapy works in treating patients with newly diagnosed Waldenstrom's macroglobulinemia.
OBJECTIVES:

 -  Determine the response rate of patients with newly diagnosed Waldenstrom's
 macroglobulinemia treated with rituximab, cyclophosphamide, doxorubicin, vincristine,
 and prednisone.

 -  Determine the associated toxic effects of this regimen, specifically the frequency of
 febrile neutropenia, in these patients.

 -  Determine the progression-free survival of patients treated with this regimen.

 -  Correlate baseline cytogenetic features and gene expression profiles with response in
 patients treated with this regimen.

 OUTLINE: This is a pilot, multicenter study.

 Patients receive rituximab intravenously (IV) over approximately 4 hours, cyclophosphamide IV
 over 5-30 minutes, doxorubicin IV over 5-15 minutes, and vincristine IV over 1 minute on day
 1. Patients also receive oral prednisone on days 1-5. Treatment repeats every 21 days for up
 to 6 courses in the absence of disease progression or unacceptable toxicity.

 Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
 annually for 5 years.

 ACTUAL ACCRUAL: A total of 16 patients were accrued for this study.
INCLUSION CRITERIA:

 -  Diagnosis of Waldenstrom's macroglobulinemia confirmed by the presence of the
 following:

 -  Bone marrow lymphoplasmacytosis with: > 10% lymphoplasmacytic cells OR aggregates
 or sheets of one of the following: lymphocytes, plasma cells or lymphoplasmacytic
 cells on the bone marrow biopsy (measured within 4 weeks prior to registration)

 -  Measurable disease defined as a quantitative immunoglobulin M (IgM) monoclonal
 protein of > 1,000 mg/dL obtained within 4 weeks prior to registration

 -  Cluster of differentiation 20 (CD20) positive stain of bone marrow or lymph node
 samples obtained < 8 weeks prior to registration

 -  Impaired bone marrow function due to infiltration by lymphoplasmacytic lymphoma,
 defined by 1 of the following:

 -  Hemoglobin no greater than 11 g/dL

 -  Serum viscosity level relative to water of at least 4.0 centipoise

 -  Absolute neutrophil count at least 1,000/mm^3

 -  Platelet count at least 75,000/mm^3

 -  Bilirubin no greater than 3.0 mg/dL

 -  Aspartate aminotransferase (AST) no greater than 3 times upper limit of normal

 -  Creatinine no greater than 3.0 mg/dL

 -  Age of 18 and over

 -  ECOG (Eastern Cooperative Oncology Group) performance status 0-1

 -  Must be symptomatic with 1 of the following:

 -  Clinically significant anemia (hemoglobin no greater than 11 g/dL)

 -  Bulky lymphadenopathy

 -  Symptoms attributable to hyperviscosity (e.g., nose bleeding, gingival bleeding,
 or retinal hemorrhage)

 -  History of heart disease allowed only if 1 of the following is demonstrated by
 echocardiography, multigated acquisition scan (MUGA), exercise MUGA, or coronary
 catheterization:

 -  Ejection fraction of at least 45%

 -  Normal fractional shortening of the left ventricle

 -  Must have been tested for hepatitis B surface antigen within 2 weeks of registration

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception

 EXCLUSION CRITERIA:

 -  Prior treatment for Waldenstrom's macroglobulinemia

 -  Prior anti-CD20 therapy

 -  Concurrent steroids exceeding 10 mg prednisone (or equivalent) per day

 -  Prior irradiation if less than 4 weeks had elapsed prior to registration and the date
 of last treatment

 -  Prior anthracyclines

 -  Prior malignancy except curatively treated basal cell or squamous cell carcinoma of
 the skin, carcinoma in situ of the cervix, or other cancer curatively treated with
 surgery alone and from which patient has been disease free for at least 5 years

 -  Active heart disease

 -  Pregnant or nursing

 -  Myocardial infarction within the past 3 months

 -  Congestive heart failure

 -  Symptomatic ventricular arrhythmia