This phase II trial is studying how well giving rituximab together with combination chemotherapy and 90-Yttrium ibritumomab tiuxetan works in treating patients with stage I or stage II lymphoma. Drugs used in chemotherapy, such as prednisone, cyclophosphamide, doxorubicin, and vincristine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab and yttrium 90-Yttrium ibritumomab tiuxetan can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Combining a monoclonal antibody with combination chemotherapy and a radiolabeled monoclonal antibody may kill more cancer cells.

PRIMARY OBJECTIVES:

I. To evaluate the complete response rate (CR) and functional CR rate in patients with previously untreated stage I (with at least 1 risk factor) or stage II CD20+ diffuse large cell lymphoma who receive therapy with R-CHOP followed by 90-Yttrium -Zevalin™.

SECONDARY OBJECTIVES:

I. To evaluate the time to treatment failure, duration of response, and overall survival in these patients who receive therapy with R-CHOP followed by 90-Yttrium -Zevalin™.

II. To evaluate the toxicity of this therapy. III. To evaluate the toxicity of adding involved field radiation therapy > 12 weeks after Zevalin™ for patients with CT+/PET+ residual masses.

TERTIARY OBJECTIVES:

I. To evaluate PET scans pre -and post - R-CHOP/Zevalin™ therapy.

OUTLINE:

R-CHOP (rituximab, prednisone, cyclophosphamide, doxorubicin,vincristine): Patients receive oral prednisone once daily on days 1-5. Patients also receive rituximab IV over several hours followed by cyclophosphamide IV, doxorubicin IV, and vincristine IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) after 2 courses receive 2 additional courses. Patients achieving a partial response, uncertain CR, or stable disease receive 4 additional courses. Patients are evaluated 3 weeks after the last course of therapy. Patients with progressive disease go off study.

Radioimmunotherapy: Beginning no more than 9 weeks after the reevaluation (or 12 weeks after the last dose of R-CHOP), patients receive rituximab IV on day 1 followed by indium In 111 ibritumomab tiuxetan IV over 10 minutes for imaging studies. Patients then receive rituximab IV followed by yttrium 90-Yttrium ibritumomab tiuxetan IV over 10 minutes on day 8.

Radiotherapy: Patients with residual disease by CT scan or positron emission tomography (PET) scan after 12 weeks after radioimmunotherapy undergo conventional involved-field radiotherapy.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually for 5 years.

Inclusion Criteria:

• Patients must have histologically confirmed diagnosis of diffuse large cell lymphoma

• Patients must be stage I or II (Modified Ann Arbor staging)

• Baseline measurements and evaluations must be obtained within 4 weeks of registration to the study; abnormal PET scans will not constitute evaluable disease unless verified by CT scan or other appropriate imaging; patients must have at least one objective measurable disease parameter (a lesion with at least 1 dimension > 1.5 cm); or if they are stage 1

• Stage I patients must have at least one of the following risk factors:

  • Age >= 60 years
  • Bulky disease (>= 5 cm in at least one dimension)
  • Elevated Lactate Dehydrogenase (LDH) above institutional upper limit of normal
  • Eastern Cooperative Oncology Group (ECOG) performance status = 2

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Absolute neutrophil count >= 1500/mm^3 (includes neutrophils and bands)

• Platelet count >= 100,000/mm^3

• Creatinine < 2.0 mg/dl

• Total bilirubin < 2 mg/dl (may be up to 3.0 mg/dl if due to liver involvement by lymphoma); patients with elevated total bilirubin should have a direct bilirubin checked; if the direct bilirubin is normal there is no need for a dose reduction

• Patients must have left ventricular ejection fraction (LVEF) of > 45%

• Patients must be tested for hepatitis B (HBV) surface antigen within 2 weeks of registration

  • NOTE: Patients who test positive will be allowed to participate but must be followed closely for clinical and laboratory signs of active HBV infection and for signs of hepatitis

Exclusion Criteria:

• Prior chemotherapy, radiation therapy, radioimmunotherapy, or immunotherapy; a short course (=< 14 days prior to registration) of corticosteroids is allowed

• Evidence of other malignancy:

  • Prior chemotherapy or prior radiation therapy for other malignancies
  • Currently receiving hormone therapy or chemotherapy for another malignancy even if the treatment is being provided in the adjuvant treatment setting, i.e. with no evidence of the original other malignancy
  • Adjuvant hormonal therapy must have been discontinued > 3 months before entering this study
  • Patients are eligible if they meet the following conditions: (a) treated carcinoma-in-situ of the cervix; (b) treated squamous cell or basal cell skin cancer; or (c) any other surgically cured malignancy from which the patient has been disease free for at least 3 years

• Pregnant or breast feeding, as there would be radiation exposure to the fetus or child; a negative pregnancy test is required =< 1 week prior to registration for women of childbearing potential (WOCBP). Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception

• Known central nervous system (CNS) lymphoma, testicular lymphoma, or vitreous lymphoma

• Known HIV infection. The safety of Zevalin™ in this population has not been tested at this time

• Serious coexisting medical condition or active infection which would compromise the ability to deliver standard R-CHOP chemotherapy

• Evidence of myelodysplasia on bone marrow aspiration and biopsy