Rituximab, Bendamustine Hydrochloride, and Lenalidomide in Treating Patients With Refractory or Relapsed Indolent Non-Hodgkin Lymphoma

10. Life expectancy ≥6 months

11. Ability to swallow oral medications

1. This study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

* Pregnant women

* Nursing women (lactating females are eligible provided that they agree not to breast feed while taking lenalidomide)

* Men or women of childbearing potential who are unwilling to employ adequate contraception

2. Active CNS lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells that requires therapy

3. Co-morbid systemic illnesses or other severe concurrent disease which, 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.

4. Prior AIDS-defining conditions. Note: HIV positive patients without history of AIDS- defining conditions are eligible

* If HIV positive, CD4 cells \< 400/mm\^3

* Current treatment with zidovudine (AZT) (which may cause overlapping adverse events, primarily myelosuppression). Patients receiving anti-retroviral therapy other than AZT are eligible

5. Uncontrolled intercurrent illness including, but not limited to:

* Ongoing or active infection

* Symptomatic congestive heart failure

* Unstable angina pectoris

* Cardiac arrhythmia

* Psychiatric illness/social situations that would limit compliance with study requirements

6. Receiving any other agent which would be considered as a treatment for the lymphoma.

Note: Prior use of rituximab is allowed.

7. Another active malignancy requiring concomitant active therapy such as radiation, chemotherapy, or immunotherapy. Exceptions to this are as follows:

* Localized non-melanotic skin cancer

* Cancers that are inactive that are being treated with hormonal therapy

* Any cancer that in the judgment of the investigator will not interfere with the study treatment plan and response assessment and require concomitant anticancer therapy for the duration of this study

Contact the study chair regarding any questions related to eligibility of patients with concomitant active malignancy

8. History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

9. History of life threatening (i.e. pulmonary embolism), DVT or recurrent thrombosis/embolism and are not on or unwilling to receive anticoagulation

* Patients with history of DVT or life threatening or recurrent thrombosis/embolism (PE) may enter the study but must receive anticoagulation with low molecular weight (LMW) heparin or therapeutic warfarin during the protocol treatment and for ≥6 months afterwards. Patients with strong family history of thrombosis should be considered for thrombophilia work up and/or anticoagulated at the discretion of treating MD.

* Patients with a prior history (\>6 months prior to study entry) of a non-life threatening, provoked thrombosis (e.g. history of catheter related thrombus or similar) and without known thrombophilia can participate in the study and receive standard prophylaxis with ASA (aspirin) or LMW heparin/warfarin at the discretion of treating MD. Active smokers should be advised on thrombosis risk and smoking cessation and may participate in the study if prophylaxis with ASA (aspirin) or LMW heparin/warfarin (at the discretion of treating MD) is given. Patients on estrogen birth control pills should be advised of the risks.

10. Known myelodysplastic syndrome

11. Receiving erythroid stimulating agents (EPO: Procrit, Aranesp). Note: Use of erythroid stimulating agents is not allowed during the study treatment.

12. Prior treatment with bendamustine.

What this study is about