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

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