Rituximab and Combination Chemotherapy in Treating Patients With Previously Untreated High- or High-Intermediate-Risk Diffuse Large B-Cell Lymphoma

This phase II trial studies how well giving rituximab together with combination chemotherapy works in treating patients with previously untreated high- or high-intermediate-risk diffuse large B-cell lymphoma (DLBCL). Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer 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 hydrochloride, vincristine sulfate, and prednisone (CHOP), work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug, combination chemotherapy, may kill more cancer cells. Giving rituximab together with combination chemotherapy together may be an effective treatment for DLBCL

PRIMARY OBJECTIVES:

I. To evaluate 1 year progression-free survival (PFS) following treatment with rituximab intense dosing and CHOP-21 (RID-CHOP) in previously untreated patients with high risk (International Prognostic Index \[IPI\] 3-5) DLBCL.

SECONDARY OBJECTIVES:

I. To evaluate, in previously untreated patients with high risk (IPI 3-5) DLBCL treated with rituximab intense dosing and CHOP-21: Complete response (CR) rate, (as defined by International Harmonization Project criteria using 18-fluorodeoxyglucose \[FDG\] -positron emission tomography \[PET\]/computed tomography \[CT\]).

II. Overall survival.

III. Toxicity profile.

IV. Rituximab pharmacokinetics for this dose and schedule.

V. Effect of immunophenotype of DLBCL on outcome.

VI. Effect of Fc-Gamma Receptor III (FcyRIII) polymorphism genotype on outcome. OUTLINE: Patients receive rituximab intravenously (IV) on days 0, 1, 4, 8, and 15 of course 1; days 1, 8, and 15 of course 2; and day 1 of all subsequent courses. Patients also receive CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1, and prednisone orally (PO) on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2-3 months for 2 years, every 6 months for 3 years, annually for up to 10 years.

Eligibility Criteria:
Inclusion Criteria:

* Newly diagnosed cluster of differentiation (CD) 20+ DLBCL with IPI between 3-5
* No prior chemotherapy, radiation therapy or immunotherapy for DLBCL; a short course (\< 2 weeks) of corticosteroids is allowed for symptom control Signed informed consent
* Eastern Cooperative Oncology Group (ECOG) Performance status assessed between 0 and 2; performance status of 3 will be accepted if impairment is caused by DLBCL complications and improvement is expected once therapy is initiated
* Measurable disease by Non-Hodgkin's Lymphoma Response Criteria on FDG-PET/CT; baseline measurements and evaluations must be obtained =\< 21 days prior to registration
* Absolute neutrophil count (ANC) \>= 1,500/μL unless due to marrow involvement by lymphoma
* Platelets \>= 75,000/μL unless due to marrow involvement by lymphoma Hemoglobin \> 7.0 g/dL unless due to marrow involvement by lymphoma
* Creatinine =\< 2.0 mg/dL or calculated creatinine clearance \>= 40
* Total bilirubin =\< 1.5 mg/dL unless due to Gilbert's disease
* Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) =\< 2.5 the upper limit of normal
* Alkaline phosphatase =\< 5x upper limit of normal
* Patients with bilirubin between 1.5-3.0 mg/dL due to lymphoma may be entered and doses adjusted
* Left ventricular ejection fraction (LVEF) \>= 50%

Exclusion Criteria:

* Women who are pregnant or breast feeding
* Known seropositivity for human immunodeficiency virus (HIV)
* Known presence of central nervous system (CNS) involvement by lymphoma
* New York Heart Association Classification III or IV heart
* Current or chronic hepatitis B or hepatitis C infection (as detected by positive testing for Hepatitis B surface Antigen \[Hbs Ag\] or antibody to Hepatitis C virus \[anti HCV\] respectively); patients must be tested for Hepatitis B surface antigen and anti-HCV =\< 21 days prior to registration
* Male patients (with female sexual partners of childbearing potential) and female patients of childbearing potential who refuse to use effective methods of contraception
* Unstable or severe uncontrolled medical, psychological, or social condition
* Any evidence of serious active, uncontrolled infection (i.e., requiring an IV antibiotic or antiviral agent)
* Receipt of live vaccine within 4 weeks prior to study drug administration
* Concurrent active malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix; subjects with previous malignancies are eligible provided that they have been treated with curative intent and remain disease free for 3 years or more
* No prior chemotherapy for lymphoma
* Prior radiation therapy for lymphoma
* Any important medical illness or abnormal laboratory finding that would, in the investigator's judgment, significantly increase the subject's risk of participating in this study