Rituximab and Combination Chemotherapy in Treating Patients With Newly Diagnosed Waldenstrom's Macroglobulinemia
Condition: Lymphoma
MeSH terms: Waldenstrom Macroglobulinemia
Intervention: rituximab; cyclophosphamide; Doxorubicin; Prednisone; Vincristine
Intervention description: Rituximab is given intravenously. The initial rate is 50 mg/hr for the 1st hour. If no toxicity, the rate may be escalated in 50 mg/hr increments at 30-minute intervals to a maximum of 400 mg/hr. If the first dose is well tolerated, the initial rate for subsequent dose is 100 mg/hr, increased in 100 mg/hr increments at 30-minute intervals, not to exceed 400 mg/hr. If the patient experiences fever and rigors, the antibody infusion is discontinued. The severity of the side effects should be evaluated. If the symptoms improve, the infusion is continued initially at half the previous rate. Following the antibody infusion, the intravenous line should be maintained for medications as needed. If there are no complications after one hour of observation, the intravenous line may be discontinued.; Cyclophosphamide will be given at a dosage of 750 mg/m² intravenously on day 1 of each cycle (1 cycle =21 days) for 6 cycles. Dose is based on surface area calculated based on actual body weight.
The drug should be administered as a rapid IV infusion over 5 to 30 minutes.; Doxorubicin will be given intravenously at a dosage of 50 mg/m² on day 1 of each cycle for 6 cycles (1 cycle =21 days). Dose is based on surface area calculated based on actual body weight.
Doxorubicin should be administered as a continuous infusion into tubing of a freely flowing intravenous line for 5 -15 minutes. Avoid extravasation.; Prednisone will be administered at 100 mg/m² orally, days 1-5 of each cycle for 6 cycles (1 cycle =21 days). Dose is based on surface area calculated based on actual body weight.; Vincristine will be administered 1.4 mg/m² intravenously (Maximum dose = 2.0 mg) on day 1 of each cycle for 6 cycles (1 cycle =21 days). Dose is based on surface area calculated based on actual body weight.
Given as IV push over 1 minute, using extravasation precautions.
Intervention MeSH terms: Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Vincristine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Waldenstrom macroglobulinemia; Rituximab; CHOP

Summary:

      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.
    

Eligibility criteria:

        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