• Response rate as assessed by complete response (CR) and partial response (PR) rates at end of treatment [ Designated as safety issue: No ]
• Event-free survival after 12 months [ Designated as safety issue: No ]
• Overall survival after 12 months [ Designated as safety issue: No ]

• Response rate as assessed by complete response (CR) and partial response (PR) rates at end of treatment
• Event-free survival after 3 months
• Overall survival after 3 months

RATIONALE: Monoclonal antibodies, such as epratuzumab and rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving monoclonal antibody therapy together with chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving monoclonal antibody therapy together with combination chemotherapy works 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.

• Biological: epratuzumab
• Biological: rituximab
• Drug: cyclophosphamide
• Drug: doxorubicin hydrochloride
• Drug: prednisone
• Drug: vincristine sulfate

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:

• 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)