This phase II trial compares the effect of the GEO-CM04S1 vaccine with the current standard of care vaccine in preventing COVID-19 infections in patients with chronic lymphocytic leukemia (CLL). The GEO-CM04S1 vaccine uses a modified vaccinia virus (MVA) backbone that may be more effective at boosting COVID-19 immunity in patients with poor immune responses. MVA strongly induces T cell expansion (infection fighting blood cells) even in the background of a suppressed immune system, which is the case in the targeted CLL patient population. Using the GEO-CM04S1 vaccine may be more effective at preventing COVID-19 infection in patients diagnosed with CLL.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
80
Undergo blood sample collection
Given IM
Given IM
City of Hope Medical Center
Duarte, California, United States
T cell response
Assessed by \>= 3-fold increase in S-specific or N-specific IFN-gamma-secreting T cells over baseline at day 56 (Primary Immune Analysis \[PIA\]), using Enzyme-linked Immunosorbent Spot (ELISPOT) assay to quantify SARS CoV-2 reactive T cells. \* Note: Missing immune response will not be imputed. Missing immune response will be categorized as no for intent-to-treat analysis but will be excluded in per-protocol analysis.
Time frame: Baseline to day 56
Incidence of adverse events (AEs) moderate toxicity (MOD)
Grade 2 AEs (based on Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0) probably or definitely attributable to vaccine boost, lasting \>= 7 days. The primary toxicity analysis will be summarized in terms of type, severity, time of onset, duration, probable association with GEO-CM04S1 vaccine and reversibility or outcome.
Time frame: From each injection to Day 28 post injection
Incidence of AEs unacceptable toxicity (UT)
Grade 3-5 AEs (based on CTCAE version 5.0) probably or definitely attributable to vaccine boost. The primary toxicity analysis will be summarized in terms of type, severity, time of onset, duration, probable association with GEO-CM04S1 vaccine and reversibility or outcome.
Time frame: From each injection to Day 28 post injection
Incidence of myocarditis or pericarditis
Any grade probably or definitely attributable to vaccine boost.
Time frame: Up to 42 days following final injection of study vaccine (GEO-CM04S1 or standard of care [SoC] mRNA-CoV-2 vaccine)
Incidence of serious adverse events (SAEs)
At least possibly related to vaccine booster injection, with the exception of hospitalization for grades 1 or 2 fever.
Time frame: From each injection to Day 365 post injection
T cell response
As assessed by \>= 3-fold increase in S-specific or N-specific IFN-gamma-secreting T cells, using ELISPOT assay to quantify SARS CoV-2 reactive T cells. Scatterplots of immune response markers across time points will be generated to visualize the temporal patterns.
Time frame: Baseline to 28 days after the second booster injection
T cell fold-increase
ELISPOT assay of SARS CoV-2 reactive T cell cytokines (IFN-gamma, IL-4).
Time frame: At all immune test time points (Baseline, and days 28, 56, 84, 112, 180 and 365)
SARS-CoV-2-S and -N specific IFNgamma (Th1) and IL-4 (Th2) cytokine levels following stimulation with overlapping peptide libraries specific for SARS-CoV-2
The immune response rate at day 112 and 90% CI will be calculated by arm. Continuous immune response markers will be summarized by means or geometric means and standard deviations if the assumption of normal distribution is not violated. Repeated immune response measurements at the multiple time points will be analyzed using generalized estimating equations (GEE) or mixed regression models. Scatterplots of immune response markers across time points will be generated to visualize the temporal patterns.
Time frame: Up to 2 years
Level of antibodies neutralizing SARS-CoV-2 Spike pseudoviruses
Based on ancestral Wuhan strain and SARS-CoV-2 variants of concern (VOC) or variants of high consequence (VHC) based on Centers for Disease Control and Prevention (CDC) definition.
Time frame: At day 56 after the first booster injection (PIA), at 28 days after the second booster injection (day 112), and at days 180 and 365
Levels of S- or N-specific IgG titers
Using quantitative enxyme-linked immunoassay (ELISA) based on World Health Organization (WHO) international standard for SARS-CoV-2 antibodies.
Time frame: At day 56 after the first booster injection (PIA), 28 days after the second booster injection (day 112), and at days 180 and 365
Confirmed COVID-19 infection by PCR viral load
Time frame: Baseline to 1 year
Severe COVID-19 infection by Food and Drug Administration (FDA) criteria
Time frame: Baseline up to 1 year
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