Lenalidomide and Vaccine Therapy in Treating Patients With Early-Stage Asymptomatic Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Inclusion Criteria:

• Patients must have histologically identified chronic lymphocytic leukemia (CLL) orsmall lymphocytic lymphoma (SLL) as defined by the World Health Organization (WHO)classification of hematopoietic neoplasms

• CLL/SLL cells must demonstrate one or more of the following high-risk genomicfeatures:

• Deletion (Del) (17p13.1) as detected by fluorescence in-situ hybridization (FISH) in > 20% of cells

• Del(11q22.3) as detected by FISH in > 20% of cells

• Complex karyotype (>= 3 cytogenetic abnormalities on stimulated karyotype)

• Unmutated immunoglobulin variable heavy chain (IgVH) (>= 98% sequence homologycompared with germline sequence)

• Patients cannot meet any of the following consensus criteria for initiatingtreatment:

• Progressive splenomegaly and/or lymphadenopathy identified by physicalexamination or radiographic studies

• Progressive lymphocytosis with total white blood cell (WBC) >= 300,000/uL

• Anemia (< 11 g/dL) or thrombocytopenia (< 100,000/uL) due to bone marrowinvolvement

• Presence of unintentional weight loss > 10% over the preceding 6 months

• National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or 3 fatigue

• Fevers > 100.5 degrees or night sweats for > 2 weeks without evidence ofinfection

• Progressive lymphocytosis with an increase of > 50% over a 2 month period or ananticipated doubling time of < 6 months

• No prior therapy for CLL/SLL, including chemotherapy, radiotherapy, and/orimmunotherapy will be allowed

• Age ≥ 18 years and < 80 years (or with justification if older than 80 years due tothe higher risk of toxicity in patients older than 80 years). CLL is rare inchildren and likely represents a different disease process. As a result, childrenare excluded from this study but may be eligible for future pediatric phase 2combination trials

• Estimated life expectancy of greater than 24 months

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

• Total bilirubin =< 1.5 times upper limit of normal (ULN) (unless secondary toGilbert disease)

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate-pyruvate transaminase [SGPT]) =< 2.5 times ULN

• Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels aboveinstitutional normal according to the Cockcroft-Gault formula

• Absolute neutrophil count (ANC) >= 1,500/uL

• Platelet count >= 100,000/uL

• Able to swallow capsules without difficulty and no history of malabsorptionsyndrome, disease significantly affecting gastrointestinal function, or resection ofthe stomach or small bowel or ulcerative colitis, symptomatic inflammatory boweldisease, or partial or complete bowel obstruction

• Females of childbearing potential (FCBP) must have a negative serum or urinepregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior toand again within 24 hours of starting lenalidomide. Further, they must either committo continued abstinence from heterosexual intercourse or begin TWO acceptablemethods of birth control: one highly effective method and one additional effectivemethod AT THE SAME TIME, at least 28 days before starting lenalidomide. FCBP mustalso agree to ongoing pregnancy testing. Men must agree to use a latex condom duringsexual contact with a FCBP, even if they have had a successful vasectomy; a FCBP isa sexually mature woman who: 1) has not undergone a hysterectomy or bilateraloophorectomy; or 2) has not been naturally postmenopausal for at least 24consecutive months (i.e., has had menses at any time in the preceding 24 consecutivemonths). All patients must be counseled at a minimum of every 28 days aboutpregnancy precautions and risks of fetal exposure

Exclusion Criteria:

• Patients who have had any treatment for their CLL/SLL, including but not limited tochemotherapy, radiotherapy, or immunotherapy, prior to entering the study

• No corticosteroid use will be permitted within two weeks prior to study, except formaintenance therapy for a non-malignant disease; maintenance therapy dose may notexceed 20 mg/day prednisone or equivalent

• Patients who meet consensus criteria for the treatment of CLL/SLL

• Patients may not be receiving any other investigational agents

• Patients with a recent history (within 6 months of study entry) of deep veinthrombosis (DVT)/pulmonary embolism (PE) are not eligible; patients with a distanthistory (greater than 6 months before study entry) of venous thromboembolic diseaseare eligible, but should receive prophylactic aspirin or low molecular weightheparin

• History of allergic reactions attributable to compounds of similar chemical orbiologic composition to thalidomide, lenalidomide or any component of PCV7 or PCV13,including the diphtheria toxoid

• Prior malignancy, except for adequately treated basal cell or squamous cell skincancer, in situ cervical cancer, or other cancer from which the subject isconsidered by his or her physician to have a 2 year survival expectation

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith study requirements

• Pregnant women are excluded from this study because lenalidomide is animmunomodulatory agent (IMID) with the potential for teratogenic or abortifacienteffects; because there is an unknown but potential risk for adverse events innursing infants secondary to treatment of the mother with lenalidomide,breastfeeding should be discontinued if the mother is treated with lenalidomide

• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviraltherapy will be eligible if they otherwise meet required hematologic parameters andare not receiving an antiviral agent with known or potential interaction withlenalidomide; because the primary aim of this study is to measure the immuneresponse to pneumococcal vaccination, only patients with CD4 cell counts >= 200 andviral load < 50 will be eligible

• Patients who have been treated for autoimmune hemolytic anemia or autoimmunethrombocytopenia within the last 6 months or are direct antiglobulin test/Coombstest or indirect antiglobulin test positive at the time of screening

• Patients who have developed erythema nodosum characterized by a desquamating rashwhile taking thalidomide or similar drugs in the past are excluded

• Because of the potential for H2-blockers to modulate antibody response topneumococcal vaccine, patients must discontinue treatment with H2-blockers (cimetidine, ranitidine, etc.) prior to beginning protocol therapy