Lenalidomide in Improving Immune Response to Vaccine Therapy in Patients With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Monoclonal B Cell Lymphocytosis
Condition: Monoclonal B-Cell Lymphocytosis; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphocytosis
Intervention: Laboratory Biomarker Analysis; Lenalidomide; Pneumococcal 13-valent Conjugate Vaccine
Intervention description: Correlative studies; Given PO; Given IM
Intervention MeSH terms: Lenalidomide; Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well lenalidomide improves immune response to
      pneumococcal 13-valent conjugate vaccine in patients with chronic lymphocytic leukemia, small
      lymphocytic lymphoma, or monoclonal B cell lymphocytosis. Biological therapies, such as
      lenalidomide, use substances made from living organisms that may stimulate or suppress the
      immune system in different ways and stop cancer cells from growing. Lenalidomide may also
      improve the effectiveness of pneumococcal 13-valent conjugate vaccine that is used to prevent
      infection.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of:

               1. CLL according to the National Cancer Institute (NCI) criteria

               2. Small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO)
                  criteria

               3. MBL according to the consensus criteria

                    -  This includes previous documentation of:

                         -  Biopsy-proven small lymphocytic lymphoma or

                         -  Diagnosis of CLL or MBL as evidenced by all of the following:

                              -  Clonal B-cell population in the peripheral blood with
                                 immunophenotyping consistent with CLL defined as:

                                   -  The population of lymphocytes share both B-cell antigens
                                      (cluster of differentiation [CD]19, CD20 [typically dim
                                      expression], or CD23) as well as CD5 in the absence of other
                                      pan-T-cell markers (CD3, CD2, etc)

                                   -  Clonality as evidenced by k (kappa) or lambda light chain
                                      expression (typically dim immunoglobulin expression) or other
                                      genetic method (e.g. immunoglobulin heavy chain variable
                                      [IGHV] analysis) NOTE: splenomegaly, hepatomegaly, or
                                      lymphadenopathy are not required for the diagnosis of CLL

                              -  Patients with a peripheral blood B-cell lymphocyte count of < 5 x
                                 10^9/L and no evidence of lymphadenopathy or organomegaly will be
                                 classified as MBL; patients with a peripheral blood B-cell
                                 lymphocyte count of < 5 x 10^9/L who have evidence of
                                 lymphadenopathy will be classified as SLL; patients with a
                                 peripheral blood B-cell lymphocyte count >= 5 x 10^9/L will be
                                 considered to have CLL

                              -  Before diagnosing MBL, CLL or SLL, mantle cell lymphoma must be
                                 excluded by demonstrating a negative fluorescence in situ
                                 hybridization (FISH) analysis for t(11;14)(IgH/cyclin D 1 [CCND1])
                                 on peripheral blood or tissue biopsy or negative
                                 immunohistochemical stains for cyclin D1 on involved tissue biopsy

          -  CLL or SLL patients only (does not apply to MBL patients): Rai stage 0-1 (both CLL and
             SLL patients can be staged using the Rai system)

          -  Patients must not previously have received the Prevnar 13 pneumococcal vaccination;
             NOTE: previous vaccination with Pneumovax (PCV23) is permitted but must have been at
             least 365 days prior to registration

          -  Patients must be previously untreated and must NOT have any of the following
             indications for chemotherapy:

               -  Evidence of progressive marrow failure as manifested by the development of or
                  worsening anemia (=< 11 g/dL) and/or thrombocytopenia (=< 100 x 10^9/L) not due
                  to autoimmune disease

               -  Symptomatic or progressive lymphadenopathy, splenomegaly or hepatomegaly

               -  One or more of the following disease-related symptoms:

                    -  Weight loss >= 10% within the previous 6 months

                    -  Extreme fatigue attributed to CLL

                    -  Fevers > 100.4 degree Fahrenheit (o^F) for 2 weeks without evidence of
                       infection

                    -  Drenching night sweats without evidence of infection Note: 1) Prior
                       chemotherapy or monoclonal antibody based therapy for treatment of CLL or
                       SLL will be considered prior therapy; nutraceutical treatments with no
                       established benefit in CLL (such as epigallocatechin gallate or EGCG, found
                       in green tea or other herbal treatments) will not be considered "prior
                       treatment" 2) Prior corticosteroid therapy for an indication other than
                       CLL/SLL will not be considered "prior treatment"; previous use of
                       corticosteroids for treatment of autoimmune complications of CLL/SLL does
                       not constitute prior therapy for CLL/SLL

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

          -  Absolute neutrophil count (ANC) >= 1000/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Hemoglobin >= 11.0 g/dL

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) unless due to Gilbert's disease;
             if total bilirubin is > 1.5 x ULN, a direct bilirubin should be performed and must be
             < 1.5 mg/dL for Gilbert's to be diagnosed

          -  Aspartate transaminase (AST) =< 3 x ULN

          -  Calculated creatinine clearance must be >= 50 ml/min using the Cockcroft-Gault formula

          -  Provide informed written consent

          -  Willing to return to enrolling institution for follow-up (during the active monitoring
             phase of the study)

          -  All study participants must be willing to be registered into the mandatory Revlimid
             Risk Evaluation and Mitigation Strategy (REMS)® program, and be willing and able to
             comply with the requirements of the REMS® program; NOTE: Actual registration in the
             Revlimid REMS® program may occur after the patient is randomized since this
             requirement only applies to patients randomized to Arm A

          -  Females of reproductive potential must be willing to adhere to the scheduled pregnancy
             testing as required in the Revlimid REMS® program; NOTE: This requirement only applies
             to patients randomized to Arm A

          -  Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients
             intolerant to acetylsalicylic acid [ASA] may use warfarin or low molecular weight
             heparin)

          -  Willing to provide blood samples for correlative research purposes

        Exclusion Criteria:

          -  Palpable lymph nodes > 3 cm in maximal dimension

          -  Any of the following:

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Any of the following comorbid conditions:

               -  New York Heart Association classification III or IV cardiovascular disease

               -  Recent myocardial infarction (=< 30 days)

               -  Uncontrolled infection

          -  Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)
             positive and currently receiving antiretroviral therapy; NOTE: patients known to be
             HIV positive, but without clinical evidence of an immunocompromised state, are
             eligible for this trial

          -  Other active primary malignancy requiring treatment or limiting survival to =< 2 years
             prior to registration

          -  Any radiation therapy =< 28 days prior to registration

          -  Any major surgery =< 28 days prior to registration

          -  Current use of corticosteroids; EXCEPTION: low doses of steroids (=< 10 mg of
             prednisone or equivalent dose of other steroid) used for treatment of nonhematologic
             medical conditions; NOTE: previous use of corticosteroids is allowed

          -  Active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic
             treatment; NOTE: patients who have a positive Coombs test but no evidence of hemolysis
             are NOT excluded from participation

          -  History of deep venous thromboses or pulmonary embolism =< 365 days prior to
             registration

          -  Co-existent diffuse large B-cell lymphoma (Richter's transformation)