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)