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.
PRIMARY OBJECTIVES: I. To assess the ability of a 6 week course of low dose lenalidomide to improve the proportion of patients with monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL) who develop an immune response to pneumococcal vaccination as measured by the proportion of patients with \>= 4-fold rise from pre-vaccine (day 15) for \>= 2 of the 3 serotypes measured at 28 days post-vaccination by opsonophagocytic activity (OPA) of antibodies from sera. SECONDARY OBJECTIVES: I. Evaluate disease status by physical exam and complete blood counts in patients participating in each arm of the study at the time of the 6 week assessment of immune response. II. Evaluate time to treatment for progressive CLL for patients on each study arm. III. Evaluate the adverse events profile in each study arm. TERTIARY OBJECTIVES: I. To assess the immune response to pneumococcal vaccination as measured by fold-change from pre-vaccine (day 15) to 28 days post-vaccination in OPA geometric mean titers (GMT) of antibodies from sera. II. To assess the immune response to pneumococcal vaccination as measured by fold-change from pre-vaccine (day 15) to 28 days post-vaccination in quantitative Streptococcus pneumoniae immunoglobulin G (IgG) GMT of antibodies from sera. III. Evaluate the effect of 6 weeks of low dose lenalidomide on global immune function including T-cell repertoire, T-cell immune synapse, serum immunoglobulin levels, and absolute numbers of T-cell and natural killer (NK) cells. OUTLINE: Patients are randomized 1 of 2 treatment arms. ARM I: Patients receive lenalidomide orally (PO) once daily (QD) on days 1-42 and pneumococcal 13-valent conjugate vaccine intramuscularly (IM) on day 15. ARM II: Patients receive pneumococcal 13-valent conjugate vaccine IM on day 15. After completion of study treatment, patients are followed up at day 28, and then every 6 months for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Correlative studies
Given PO
Given IM
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
Mayo Clinic
Rochester, Minnesota, United States
Proportion of Participants With Successful Response
Rate of response to pneumococcal 13-valent conjugate vaccine defined as a four-fold rise from baseline to 28 days after immunization (day 43) for \>= 2 of the 3 serotypes studied by OPA of antibodies from sera. The proportion of successes will be estimated in each arm by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated in each arm based on the normal approximation.
Time frame: Day 43
Disease Status by Physical Exam and Complete Blood Counts
The distribution of disease status will be evaluated in each arm and will be summarized descriptively. Patients will be classified as responders (complete clinical response, incomplete marrow recovery, partial response) vs. non-responders (stable disease, progressive disease \[PD\]). For MBL, patients will be classified as not PD vs PD. Differences in disease status response will be compared between the two arms using Fisher's exact test.
Time frame: At 6 weeks
Incidence of Adverse Events Using NCI Common Terminology Criteria for Adverse Events Version 4.0
Adverse Events were collected during treatment according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The maximum grade for each type of adverse event will be recorded for each patient. The worst grade per patient is presented below.
Time frame: Up to day 50
Time to Treatment for Progressive CLL
The distribution of time to treatment will be estimated in each arm using the method of Kaplan-Meier. Time to treatment will be compared between the two arms using log-rank statistics.
Time frame: Time from the date of registration to the date of initiation of treatment for progressive CLL assessed up to 2 years
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