Phase II Study of Lenalidomide to Repair Immune Synapse Response and Humoral Immunity in Early-Stage, Asymptomatic Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) With High-Risk Genomic Features
I. To determine the proportion of early-stage, high-risk chronic lymphocytic leukemia (CLL)
patients achieving a response (≥ 4-fold increase from baseline and/or antibody
concentrations ≥ 0.35 μg/mL in 6 of 7 type-specific anti-pneumococcal antibody levels) after
2 doses of pneumococcal 13-valent conjugated vaccine (Prevnar 13, PCV13) administered
concurrently versus sequentially with low-dose lenalidomide.
I. To determine the complete response (CR) rate after 2 years of lenalidomide therapy.
II. To determine the time to first treatment (TFT), defined as the time from diagnosis to
first non-lenalidomide therapy for progressive CLL as described by IWCLL 2008 criteria.
III. To determine the incidence of infection and invasive pneumococcal infections following
treatment with the PCV13 vaccine and either concurrent or sequential lenalidomide.
IV. To determine the frequency of humoral and cellular immune response to CLL tumor antigens
following treatment with the PCV13 vaccine and either concurrent or sequential lenalidomide.
V. To determine the safety and toxicity associated with long-term lenalidomide exposure.
VI. To perform correlative pharmacodynamic and pharmacokinetic studies and correlate these
with vaccine/tumor immunologic and disease response.
OUTLINE: Patients are stratified according to prior exposure to pneumococcal vaccination
within the past 5 years (yes vs no). Patients are randomized to 1 of 2 treatment arms.
ARM I (concurrent PCV13): Patients receive low-dose lenalidomide orally once daily on days
1-28. Treatment repeats every 28 days for at least 24 courses in the absence of disease
progression or unacceptable toxicity. Patients also receive 13-valent protein-conjugated
pneumococcal vaccine (PCV13) intramuscularly (IM) on days 78 and 134 (courses 3 and 5).
ARM II (sequential PCV13): Patients receive PCV13 IM on days 1 and 78 (courses 1 and 3).
Patients also receive low-dose lenalidomide as in arm 1 beginning on day 106 (course 4).
Blood samples are collected at baseline and periodically during study for humoral and
cellular immune response and pharmacokinetic and pharmacodynamic studies.
After completion of study treatment, patients are followed up every 3 months for 1 year and
then every 6 months thereafter.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Proportion of patients who achieve an antibody response
Defined as achieving at least a four-fold increase in post-vaccination serotype-specific IgG titers or serotype-specific IgG concentrations of >= 0.35 ug/mL for 6 of 7 serotypes measured by a standard ELISA assay.
Up to 1 month
Ohio State University
United States: Food and Drug Administration
|Ohio State University Medical Center||Columbus, Ohio 43210|