sars-cov-2 vaccine (geo-cm04s1) versus mrna sars-cov-2 vaccine in patients with blood cancer

Conditions: COVID-19 Infection; Hematopoietic and Lymphoid System Neoplasm; Leukemia; Lymphoma; Plasma Cell Myeloma

Summary: this phase 2 trial studies the immune response to geo-cm04s1 (previously designated as coh04s1) compared to standard of care (soc) mrna sars-cov-2 vaccine in patients with blood cancer who have received stem cell transplant or cellular therapy. geo-cm04s1 belongs to a category called modified vaccinia ankara (mva) vaccines, created from a new version of mva, called synthetic mva. geo-cm04s1 works by inducing immunity (the ability to recognize and fight against an infection) to sars-cov-2. the immune system is stimulated to produce antibodies against sars-cov-2 that would block the virus from entering healthy cells. the immune system also grows new disease fighting t cells that can recognize and destroy infected cells. giving geo-cm04s1 after cellular therapy may work better in reducing the chances of contracting coronavirus disease 2019 (covid-19) or developing a severe form of covid-19 disease in patients with blood cancer compared to soc mrna sars-cov-2 vaccine.

primary objective: i. evaluate the biological activity and the role of timing of 2 injections of geo-cm04s1 vaccine administered at 2.5e8 pfu/dose compared to soc mrna vaccine. secondary objectives: i. assess safety of geo-cm04s1 vaccine. ii. evaluation of sars-cov-2 s and n-specific th1 vs th2 polarization. iii. evaluate t-cell levels and function. iv. evaluate activated/cycling and memory phenotype markers. v. evaluate durability of immune responses. vi. evaluate maintenance of immunity that can be associated with protection over the study period. exploratory objective: i. surveillance for incidental covid-19 infection during follow-up (1 year). outline: patients are randomized to 1 of 2 arms. arm i : patients receive one dose of geo-cm04s1 intramuscularly (im) in the upper arm on days 0 and 28. arm ii : patients receive one dose of soc mrna sars-cov-2 vaccine im in the upper arm on days 0 and 28. after the completion of study treatment, patients are followed up at days 7, 90, 120, 180, and 365.

Eligibility criteria:
inclusion criteria: * documented informed consent of the participant * age \>=18 years * eastern cooperative oncology group (ecog) =\<1 * allogeneic or autologous hematopoietic cell transplant (hct), cellular therapy (chimeric antigen receptor \[car\] t-cell) recipients who are at \>= 3 months of infusion date of respective regimen * platelets \>= 50,000/mm\^3 (to be performed within 30 days prior to day 0 of protocol therapy unless otherwise stated) * white blood cells (wbcs) \>= 1000/mm\^3 (to be performed within 30 days prior to day 0 of protocol therapy unless otherwise stated) * total bilirubin \< 1.5 x upper limit of normal (uln) (to be performed within 30 days prior to day 0 of protocol therapy unless otherwise stated) * aspartate aminotransferase (ast) \< 2.5 x uln (to be performed within 30 days prior to day 0 of protocol therapy unless otherwise stated) * alanine aminotransferase (alt) \< 2.5 x uln (to be performed within 30 days prior to day 0 of protocol therapy unless otherwise stated) * creatinine \< 1.5 x uln (to be performed within 30 days prior to day 0 of protocol therapy unless otherwise stated) * negative covid-19 pcr test * women of childbearing potential (wocbp): negative urine or serum pregnancy test (to be performed within 30 days prior to day 0 of protocol therapy unless otherwise stated). if the urine pregnancy test is inconclusive 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 dose of protocol therapy * 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: * systemic corticosteroids required for chronic conditions at doses \> 0.5mg/kg/day prednisone equivalent within 7 days of enrollment * prior evusheld or other anti-sars cov-2 prophylaxis \< 2 weeks prior to enrollment * therapies that cause profound t-cell or b cell depletion within 30 days of enrollment * maintenance therapies (e.g. rituximab, bruton tyrosine kinase inhibitors, janus kinase inhibitors) within 30 days of enrollment * received investigational or licensed sars-cov-2 vaccines after their qualifying cellular therapy. patients who received a sars- cov-2 vaccine prior to cellular therapy are eligible for this trial, as revaccination for these patients (e.g. flu and shingles vaccine) is standard of care. * received a live vaccine ≤30 days prior to administration of study vaccine or subjects who are =\ 2 weeks before the first injection and \> 2 weeks post 2nd injection * history of allergic reactions attributed to compounds of similar chemical or biologic composition to vaccine agents * history of adverse event with a prior smallpox vaccination * any mva vaccine or poxvirus vaccine in the last 12 months * history (suspected or confirmed) of myocarditis or pericarditis * clinically significant uncontrolled illness * females only: pregnant or breastfeeding * any other condition that would, in the investigator's judgment, contraindicate the subject'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) * anyone considered to be in a vulnerable population as defined in 45 cfr §46.111 (a)(3) and 45 cfr §46, subparts b-d