A Vaccine Booster (GEO-CM04S1) for the Prevention of COVID-19 in Patients With Chronic Lymphocytic Leukemia

PRIMARY OBJECTIVE: I. Estimate the T cell-based immune response rate on day 56 post-injection of synthetic MVA-based SARS-CoV-2 vaccine COH04S1 (GEO-CM04S1) vaccine boost administered at 2.5x10\^8 plaque-forming unit (PFU) or standard of care (SOC) vaccine administered as standard of care. SECONDARY OBJECTIVES: I. Evaluate the safety of single-dose vaccine boost based on moderate and unacceptable toxicities up to day 28 post-injection for the GEO-CM04S1 and SOC vaccines. II. Estimate the T cell-based immune response rate at day 112 post-injection of GEO-CM04S1 vaccine at 2.5x10\^8 PFU vs SOC severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger ribonucleic acid (mRNA) vaccine administered as COVID-19 vaccine boosters. III. Select the more promising vaccine to study further as a booster in patients with CLL. IV. Evaluate SARS-CoV-2 S and N-specific Th1 vs Th2 polarization. V. Estimate the magnitude and durability of T-cell-based immune responses over a 12-month period. VI. Estimate the levels and durability of SARS-CoV-2-specific IgG in a 12-month period. VII. Evaluate levels of antibodies neutralizing SARS-CoV-2 in original strain and in variants of concern (VOC) based on the Centers for Disease Control and Prevention (CDC) definition using Spike-pseudotyped lentivirus. VIII. Evaluate the overall safety profile during follow-up (12 months). IX. Estimate the incidence and severity of COVID-19 infection during follow-up (12 months). EXPLORATORY OBJECTIVES: I. Determine the SARS-CoV-2 variant by sequencing virus from polymerase chain reaction (PCR)-confirmed infected participants. II. Evaluate activated/cycling and memory phenotype markers in SARS-CoV-2 stimulated T cells. III. Estimate SARS-CoV-2-specfic serum IgA levels measured by enzyme-linked immunoassay (ELISA). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive GEO-CM04S1 vaccine intramuscularly (IM) on days 0 and 84 on study. ARM II. Patients receive mRNA vaccine injection IM on days 0 and 84 on study. Patients undergo blood sample collections throughout the study and are monitored for 1 year.