A Phase II Study of Lenalidomide (REVLIMID®) in Combination With Rituximab for Patients With CD5+/CD20+ Hematologic Malignancies Who Relapse or Progress After Rituximab

Inclusion Criteria:

- Have histologically or cytologically confirmed CD5+/CD20+ B-Cell Chronic Lymphocytic
Leukemia or Mantle Cell Lymphoma

- Meet the following CLL criteria to participate in this study:

- Absolute lymphocyte count > 5000/μL

- CD20+ and CD5+

- Atypical cells representing < 55% on the peripheral smear

- Bone marrow lymphocytes ≥ 30%

- Or previous confirmed diagnosis of CLL/small lymphocytic lymphoma (SLL) with
less than 5000/μl or less than 30% lymphocytes in BM

- CLL Patients are eligible if they have stage III or IV disease. Patients with stage
0, I or II disease will be eligible if they have evidence of active disease defined
as one or more of the following signs/symptoms:

- Documented weight loss of ≥ 10% over a six month period

- Febrile episodes of 38 degrees Celsius (100.5 degrees F) or greater for greater
than 2 weeks without evidence of infection

- Massive or progressive splenomegaly defined as > 6 cm below the left costal
margin

- Massive (> 10 cm in longest diameter) or progressive lymphadenopathy

- Patients with progressive lymphadenopathy will need a biopsy of the lymphadenopathy
within the previous six months to ensure that the disease entity remains chronic
lymphocytic leukemia. Lymph node biopsy can be deferred if the patient does not have
superficial lymphadenopathy that is easily accessible by surgery or by CT guided
biopsy.

- The diagnosis of MCL is based upon the National Comprehensive Cancer Network (NCCN)
guidelines. The patient's will have biopsy proven CD5+/CD20+/CD23- mantle cell
lymphoma with the characteristic cytogenetic abnormality t(11;14) or a cyclin D1
positive immunophenotype. If malignancy is CD23+ but FISH positive for t(11;14),
diagnosis of mantle cell lymphoma can be made. Patients with mantle cell lymphoma
require appropriate staging which would include upper and lower endoscopy within 2
months of enrollment per NCCN guidelines without additional treatment since the
endoscopies.

- Patients with MCL and CLL will be eligible if they have relapsed or progressive
disease after Rituximab therapy or a combination therapy including Rituximab. Any
other number of previous treatments is allowed including autologous or allogeneic
bone marrow transplantation. Patients who are younger than age 65 who have not had a
bone marrow transplant must be ineligible or have declined a bone marrow (BM)
transplant to participate in this study. Although a transplant is not the standard of
care for this patient population, it does provide the best opportunity for a cure.

- Anticipated life expectancy of > 3 months

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

- Baseline organ and marrow function as follows:

- Absolute neutrophil count ≥1,500/µL

- Platelets ≥50,000/µL

- Total bilirubin ≤2.0 mg/dL (34 µmol/L)

- aspartic transaminase (AST)/alanine transaminase (ALT) ≤2.5 X institutional
upper limit of normal(ULN)

- Creatinine < institutional ULN OR

- Creatinine clearance ≥60 mL/min/m² for patients with creatinine levels above
institutional ULN

- All study participants must be registered into the mandatory RevAssist® program, and
be willing and able to comply with the requirements of RevAssist®. Women of
childbearing potential, and men with a partner of childbearing potential must follow
pregnancy test and birth control guidelines outlined for this study.

- Ability to understand and the willingness to sign a written informed consent document

- Able to adhere to the study visit schedule and other protocol requirements

- Patients with uric acid levels > ULN at baseline must be corrected to ≤ULN prior to
the initiation of study therapy.

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering study or those who have not recovered
from adverse events due to agents administered more than 4 weeks earlier.

- May not be receiving any other investigational agents

- Known brain metastases

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to lenalidomide and/or thalidomide

- Prior desquamating (blistering) rash with thalidomide

- Neuropathy ≥ grade 2

- Uncontrolled intercurrent illness including (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.

- Women currently pregnant or breastfeeding

- Known seropositive for or active viral infection with human immunodeficiency virus
(HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are
seropositive because of hepatitis B virus vaccine are eligible.

- History of another malignancy besides CLL or MCL who have been disease-free ≤ 3 years
with exception of basal cell or squamous cell carcinoma of skin or carcinoma in situ
of cervix or breast

- Any serious medical condition or psychiatric illness that will prevent patient from
signing the informed consent form or will place the patient at unacceptable risk if
he/she participates in the study

- Prior use of lenalidomide

- Prior severe hypersensitivity to Rituximab or other murine products