a vaccine booster (geo-cm04s1) for the prevention of covid-19 in patients with chronic lymphocytic leukemia

Conditions: Chronic Lymphocytic Leukemia; COVID-19 Infection

Summary: 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.

Eligibility criteria:
inclusion criteria: * documented informed consent of the participant and/or legally authorized representative * age: \>= 18 years * eastern cooperative oncology group (ecog) =\< 1 * histologically confirmed diagnosis of cll according to world health organization (who) classification * prior covid-19 vaccination (2 or more pfizer or moderna) with last injection \>= 3 months prior * fully recovered from the acute toxic effects (except alopecia) to =\< grade 1 to prior anti-cancer therapy * white blood cells (wbc) \>= 1,000/mm\^3 (to be performed within 14 days prior to day 1 of protocol therapy) * platelets \>= 50,000/mm\^3 (to be performed within 14 days prior to day 1 of protocol therapy) * total bilirubin =\< 1.5 x upper limit of normal (uln) (unless has gilbert's disease) (to be performed within 14 days prior to day 1 of protocol therapy) * aspartate aminotransferase (ast) =\< 2.5 x uln (to be performed within 14 days prior to day 1 of protocol therapy) * alanine transaminase (alt) =\< 2.5 x uln (to be performed within 14 days prior to day 1 of protocol therapy) * creatinine clearance \<1.5 uln (to be performed within 14 days prior to day 1 of protocol therapy) * women of childbearing potential (wocbp): negative urine or serum pregnancy test (to be performed within 14 days prior to day 1 of protocol therapy) * if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 weeks after the last vaccine injection * childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only) exclusion criteria: * known current sars cov-2 infection * prior evusheld or other anti-sars cov-2 prophylaxis \< 2 weeks prior * prior hematopoietic cell transplantation (hct) or chimeric antigen receptor (car) t cell therapy within the previous year * systemic corticosteroids required for chronic conditions at doses \> 0.5mg/kg/day prednisone equivalent within 7 days of enrollment * intensive cytotoxic therapies, t-cell depleting therapies, within 30 days of enrollment; however, patients with stable disease on maintenance therapies are allowed (see conmeds for lists of acceptable and contraindicated therapies) * participants who have had a live vaccine =\ 2 weeks before a study vaccine injection and \> 2 weeks post study vaccine injection * history of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent (e.g., egg allergies) * active infection not controlled on appropriate therapy * history of adverse event with a prior smallpox vaccination * history of pericarditis or myocarditis * any mva vaccine or poxvirus vaccine in the last 12 months * females only: pregnant or breastfeeding * any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures * prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)