Phase I/II Study of Lenalidomide (Revlimid), Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R2CHOP) Chemoimmunotherapy in Patients With Newly Diagnosed Diffuse Large Cell and Follicular Grade IIIA/B B Cell Lymphoma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed diffuse large cell or grade 3A/B follicular lymphoma

- Newly diagnosed disease

- Stage II, III, or IV disease

- Measurable disease, defined as ≥ 1 lesion ≥ 1.5 cm in one diameter, as detected by CT
scan or PET-CT scan (PET/CT fusion)

- CD20-positive disease

- No post-transplant lymphoproliferative disorder (PTLD)

- No CNS lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) OR direct bilirubin normal

- Alkaline phosphatase ≤ 3 times ULN (5 times ULN if direct liver involvement by
lymphoma)

- AST ≤ 3 times ULN (5 times ULN if direct liver involvement by lymphoma)

- Creatinine ≤ 2 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile female patients must use effective double-method contraception for ≥ 28 days
before, during, and for ≥ 28 days after completion of study therapy

- Fertile male patients must use effective contraception during and for ≥ 28 days after
completion of study therapy, even if they have had a successful vasectomy

- No blood, sperm, or semen donation during and for ≥ 28 days after completion of study
therapy

- Willing to return to enrolling institution for follow-up

- Willing to provide blood samples for translational research purposes

- No comorbid systemic illness or other severe concurrent disease that, in the judgment
of the investigator, would preclude study entry or significantly interfere with the
proper assessment of safety and toxicity of the prescribed study regimen

- No known HIV positivity

- Not immunocompromised

- No concurrent uncontrolled illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness/social situation that would preclude compliance with study
requirements

- No other active malignancy, except localized nonmelanotic skin cancer or any cancer
that, in the judgment of the investigator, has been treated with curative intent and
will not interfere with the study treatment plan and response assessment

- No myocardial infarction within the past 6 months

- No congestive heart failure requiring ongoing maintenance therapy for
life-threatening ventricular arrhythmias

- Ejection fraction ≥ 45% by MUGA or ECHO

- No history of life threatening or recurrent thrombosis/embolism (unless on
anticoagulation therapy during study treatment)

PRIOR CONCURRENT THERAPY:

- No prior radiotherapy to ≥ 25% of the bone marrow

- No concurrent erythroid-stimulating agents (e.g., Procrit, Aranesp)

- No other concurrent treatment for lymphoma

- No concurrent radiotherapy, chemotherapy, or immunotherapy for another active
malignancy

- Able to receive concurrent prophylactic anticoagulation therapy (e.g., low-dose
aspirin [81 mg] daily or an alternative prophylaxis [e.g., warfarin or low molecular
weight heparin])