Monoclonal Antibody Therapy and Combination Chemotherapy in Treating Patients With Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

OBJECTIVES:> Primary>

• Assess the efficacy of epratuzumab and rituximab in combination with cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (CHOP), as measured by 12-month, event-free survival, in patients with previously untreated stage II, III, or IV diffuse large B-cell lymphoma.>
• Assess the use of positron emission tomography (PET) scan routinely early in treatment and after completion of treatment.>
• Assess the functional response rate (complete response, partial response, or stable disease by CT scan and PET negative) in patients treated with this regimen.>
• Assess the safety of this treatment regimen.> Secondary>
• Correlate laboratory prognostic factors for large cell lymphoma with clinical response to this regimen.> OUTLINE: This is a multicenter study.> Patients receive epratuzumab IV over 1 hour on day 1, rituximab IV over 4-8 hours on day 1 or days 1 and 2, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1 or 2, and oral prednisone on days 1-5 or 2-6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.> After completion of study treatment, patients are followed periodically for up to 5 years.> PROJECTED ACCRUAL: A total of 86 patients will be accrued for this study.>

DISEASE CHARACTERISTICS:

• Histologically confirmed diffuse large B-cell lymphoma

• B-cell phenotype (CD20+) as determined by immunohistochemistry (IHC) or flow cytometry
• Stage II, III, or IV disease
• CD22+ tumor by IHC*

NOTE: *CD22 status may be determined after study enrollment

• Measurable disease, defined as at least 1 lesion ≥ 1.5 cm by CT scan or physical exam
• No relapsed or refractory non-Hodgkin's lymphoma
• No history of transformed lymphoma
• No CNS lymphoma

• CNS symptoms or bone marrow or sinus involvement must have absence of CNS lymphoma confirmed by lumbar puncture

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-3

• For patients with ECOG PS 3, the PS must be disease related
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Total bilirubin ≤ 2 mg/dL (if total bilirubin > 2 mg/dL, direct bilirubin should be within normal limits)
• AST ≤ 3 times upper limit of normal (ULN) (5 times ULN if there is liver involvement)
• Creatinine ≤ 2 times ULN
• Life expectancy ≥ 12 weeks
• Negative pregnancy test
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 12 months after completion of study treatment
• No active serious infection requiring antibiotics
• No New York Heart Association class III or IV heart disease
• No other primary malignancy within the past 5 years, except for squamous cell or basal cell carcinoma of the skin, in situ carcinoma of the cervix, or previously treated prostate cancer with a stable prostate-specific antigen
• No known HIV positivity
• No known hepatitis B or C infection
• Ejection fraction ≥ 45% by MUGA or echocardiogram (required if patients has a history of heart disease or is ≥ 50 years old)
• Willing to provide blood and tissue samples for mandatory translational research component of study

PRIOR CONCURRENT THERAPY:

• No prior therapy for diffuse large B-cell lymphoma, including the following:

• Chemotherapy
• Immunotherapy
• Biologic therapy
• Radiotherapy
• Prior short course (≤ 14 days) of corticosteroids allowed
• Prior splenectomy allowed
• No prior pelvic irradiation
• No other concurrent investigational agents
• No concurrent chemotherapy, immunotherapy, or radiotherapy
• No concurrent enrollment on another treatment study involving a pharmacologic agent (e.g., drugs, biologics, immunotherapy, or gene therapy)