Everolimus, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Untreated Diffuse Large B-Cell Lymphoma

DISEASE CHARACTERISTICS:

* Untreated, histological diagnosis of CD20-positive diffuse large B-cell lymphoma
* Stage II-IV (Ann Arbor Staging)
* Measurable or assessable disease defined as at least one of the following:

  * A lymph node or tumor mass that is ≥ 2.0 cm in at least one dimension by CT portion of PET/CT scan, CT scan, or MRI
  * Diffuse infiltration of an organ such as the stomach, bone marrow, peripheral blood, liver, lungs, or bowel by lymphoma without a discrete mass would constitute assessable, but not measurable, disease
* Diagnostic tissue slides and paraffin-embedded block must be available
* No CNS lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Absolute neutrophil count (ANC) ≥ 1,500/mm³
* Peripheral platelet count ≥ 100,000/mm³
* Hemoglobin (HgB) \> 9.0 g/dL
* Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

  * For total bilirubin \> 1.5 times ULN, the direct bilirubin must be normal
* Alkaline phosphatase ≤ 3 times ULN (≤ 5 times ULN if evidence of direct liver involvement by lymphoma)
* AST ≤ 3 times ULN (≤ 5 times ULN if evidence of direct liver involvement by lymphoma)
* Creatinine ≤ ULN
* Negative serum or urine pregnancy test
* Not pregnant or nursing
* Men or women of childbearing potential must be willing to employ adequate contraception throughout the study and for12 months after the last dose of study drug
* Willing to return to the National Central Cancer Treatment Group (NCCTG) enrolling institution for follow-up
* Willing to provide archival tissue from the primary diagnosis (original lymphoma lymph node tissue biopsy)
* Willing to abstain from eating grapefruit or drinking grapefruit juice for the duration of the study
* Diabetic patients who are taking insulin or oral anti-diabetic therapy must have HbA1c ≤ 8%, or a fasting serum glucose ≤ 110% ULN
* HIV-positive patients must have CD4 count ≥ 400/mm³
* No co-morbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
* No immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be HIV positive with a CD4 count of \< 400/mm³
* No uncontrolled intercurrent illness including, but not limited to, any of the following:

  * Ongoing or active infection
  * Symptomatic congestive heart failure
  * Unstable angina pectoris
  * Cardiac arrhythmia
  * Severely impaired lung function
  * Uncontrolled diabetes as defined by fasting serum glucose \> 1.5 times ULN

    * Optimal glycemic control should be achieved before starting trial therapy
  * Psychiatric illness/social situations that would limit compliance with study requirements
  * Liver disease such as cirrhosis or severe hepatic impairment
  * Chronic active hepatitis
  * Chronic persistent hepatitis or history of hepatitis B or C
* No other active malignancy except non-melanotic skin cancer or carcinoma in situ of the cervix

  * If there is a history of prior malignancy, patients must not be receiving other specific treatment (other than hormonal therapy) for their cancer
* No positive hepatitis B antigen (HBsAg) or hepatitis C serology (HCV) tests meeting the following criteria:

  * Hepatitis B surface antigen (HbsAg) and antibody to hepatitis B core (anti-HBc) or hepatitis C antibody
  * All patients must be screened prior to registration
  * Patients who have evidence of chronic or acute infection with either hepatitis B or C may not be treated on this protocol

PRIOR CONCURRENT THERAPY:

* Not receiving any other investigational agent that would be considered as a treatment for the primary neoplasm
* No planned immunization with attenuated live vaccines ≤ 7 days prior to registration or during study period

  * Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus
  * Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines
* Not currently on enzyme-inducing anti-convulsants or other strong inducers of CYP3A4 (efavirenz, nevirapine, barbiturates, carbamazepine, modafinil, phenobarbital, phenytoin, rifabutin, rifampin, pioglitazone, or St. John wort) or strong inhibitors of CYP3A4 (indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, saquinavir, or telithromycin)