Rituximab, Romidepsin, and Lenalidomide in Treating Patients With Recurrent or Refractory B-cell Non-Hodgkin Lymphoma

Exclusion Criteria

• •PHASE II: Histological confirmation of transformation of FL lymphoma to diffuse large B cell lymphoma or aggressive lymphoma
• •The biopsy confirming diagnosis can be up to 12 weeks prior to registration as long as there is no intervening therapy; note: if patient has had lymphoma treatment since previous biopsy, a biopsy should be repeated
• •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• •Measurable disease (at least 1 lesion of \>= 1.5 cm in diameter) as detected by computed tomography (CT) or the CT images of the positron emission tomography (PET)/CT
• •Absolute neutrophil count (ANC) \>= 1500/mm\^3
• •Platelet count \>= 75,000/mm\^3
• •Total bilirubin =\< 1.5 x upper limit of normal (ULN) or if total bilirubin is \> 1.5 x ULN, the direct bilirubin =\< ULN
• •Alkaline phosphatase =\< 3 x ULN unless due to direct lymphoma involvement, and then =\< 5 x ULN
• •Aspartate transaminase (AST) =\< 3 x ULN unless due to direct lymphoma involvement, and then =\< 5x ULN
• •Calculated creatinine clearance \>= 50 mL/min using the Cockcroft-Gault formula
• •Magnesium \>= 1.6 mg/dL
• •Potassium \>= 3.5 mg/dL
• •Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid Risk Evaluation and Mitigation Strategy (REMS)® program
• •Willing to be registered into the mandatory Revlimid REMS® program, and willing and able to comply with the requirements of the REMS® program
• •Life expectancy \>= 3 months
• •Ability to complete medication diary by themselves or with assistance
• •Ability to provide informed written consent
• •Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• •* Note: during the active monitoring phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
• •Willing to provide tissue for central review and blood samples for correlative research purposes
• •Prior therapy with histone deacetylase (HDAC) inhibitors or immunomodulatory drugs (IMDs) (lenalidomide or thalidomide)
• •Any of the following:
• •* Pregnant women
• •* Nursing women
• •* Men or women of childbearing potential who are unwilling to employ adequate contraception
• •Active central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells that requires therapy
• •Prolongation of corrected QT interval of \> 480 ms
• •History of myocardial infarction =\< 6 months prior to registration, unstable angina, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
• •History of life threatening or recurrent thrombosis/embolism; patients may participate if they are on anticoagulation during the treatment
• •Receiving erythroid stimulating agents (erythropoietin \[EPO\]: Procrit, Aranesp)
• •History of allogeneic bone marrow or stem cell transplantation