A Pilot/Feasibility Phase I Study of Bendamustine, Rituximab and Lenalidomide in Patients With Refractory/Relapsed Indolent NHL

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed relapsed (recurrent after previous therapies) or refractory
(no response to previous therapy), indolent/low-grade B-cell non-Hodgkin lymphoma
(NHL) expressing CD20 antigen

- Small lymphocytic lymphoma (SLL) excluding chronic lymphocytic leukemia (CLL)
(patients with peripheral blood lymphocyte count > 5,000/mm³)

- Follicular lymphoma, grades 1, 2 (grade 3 excluded)

- Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphatic tissue
(MALT) type

- Lymphoplasmacytic lymphoma including Waldenstrom macroglobulinemia

- The biopsy-confirming relapse can be up to 12 weeks prior to registration as long as
there is no intervening therapy; if patients have been on active treatment within
last 12 weeks, the tumor biopsy must be repeated before study enrollment to evaluate
for transformation

- 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 (PET)/CT

- Patients with Waldenstrom macroglobulinemia are not required to have measurable
disease by CT or PET/CT if monoclonal protein is detectable by serum protein
electrophoresis and/or IgM level is at least 2 times upper limit of normal

- No active CNS lymphoma or cerebrospinal fluid involvement with malignant lymphoma
cells that requires therapy

- No known myelodysplastic syndrome

PATIENT CHARACTERISTICS:

- ECOG performance status 0, 1, or 2

- Life expectancy ≥ 6 months

- ANC ≥ 1,500/mL

- Platelet count ≥ 100,000/mL

- Total bilirubin ≤ 1.5 times institutional upper limit of normal (ULN) OR, if total
bilirubin is > 1.5 times ULN, the direct bilirubin must be normal

- SGOT (AST) ≤ 5 times ULN

- Creatinine clearance ≥ 50 mL/min

- All study participants must be registered into the mandatory RevAssist® program, and
be willing and able to comply with the requirements of RevAssist®

- Females of childbearing potential (FCBP) must have:

- A negative serum or urine pregnancy test with a sensitivity of at least 25
mIU/mL ≤ 10 - 14 days prior to registration and again ≤ 24 hours prior to
starting course 1 of lenalidomide

- ≥ 28 days prior to registration, throughout the duration of the study, and
for up to 28 days from the last dose of lenalidomide, FBCP must agree to
either continued abstinence from heterosexual intercourse or must begin TWO
acceptable methods of birth control, one highly effective method and one
additional effective method AT THE SAME TIME

- Must agree to ongoing pregnancy testing throughout the duration of the
study and for up to 28 days from the last dose of lenalidomide

- Men must agree to abstinence or to use a latex condom during sexual contact with
a FCBP even if they have had a successful vasectomy

- Willing to return to North Central Cancer Treatment Group (NCCTG) enrolling
institution for follow-up

- Ability to swallow oral medications

- If currently not on anticoagulation medication, willing and able to take low-dose
aspirin (81 mg) daily

- Any of the following not allowed:

- 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

- 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 prior AIDS-defining conditions

- HIV-positive patients without history of AIDS-defining conditions are eligible
if CD4 cells < 400/mm³

- No 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

- No other 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 or require concomitant
anticancer therapy for the duration of this study

- No history of myocardial infarction ≤ 6 months or congestive heart failure requiring
use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

- Patients with a history of life-threatening (i.e., pulmonary embolism), deep vein
thrombosis (DVT), or recurrent thrombosis/embolism who are not on or unwilling to
receive anticoagulation are excluded

- 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 a 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 aspirin or LMW heparin/warfarin at
the discretion of treating MD

PRIOR CONCURRENT THERAPY:

- If currently not on anticoagulation medication, willing and able to take low-dose
aspirin (≥ 81 mg) daily

- The dose of aspirin should be a minimum of 81 mg and can be higher if the
patient is on the agent for other reasons

- If aspirin is contraindicated, the patient may be considered for the study after
consultation with the study chair regarding other alternatives, including the
possible use of warfarin or low molecular weight heparin

- Patients unable to take any prophylaxis are not eligible

- HIV-positive patients with no prior AIDS-defining conditions must not be on current
treatment with zidovudine (AZT)

- Patients receiving antiretroviral therapy other than AZT are eligible

- Not receiving any other agent which would be considered as a treatment for the
lymphoma

- Prior use of rituximab is allowed

- Not receiving erythroid-stimulating agents (EPO: Procrit, Aranesp); use of
erythroid-stimulating agents is not allowed during the study treatment

- No prior treatment with bendamustine hydrochloride