SARS-CoV-2 Vaccine (GEO-CM04S1) Versus mRNA SARS-COV-2 Vaccine in Patients With Blood Cancer

Prior treatment

• 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 within administration of inactivated vaccines (e.g. influenza vaccine). Flu shots are allowed \> 2 weeks before the first injection and \> 2 weeks post 2nd injection
• History of adverse event with a prior smallpox vaccination
• Any MVA vaccine or poxvirus vaccine in the last 12 months

Other illness

• Systemic corticosteroids required for chronic conditions at doses \> 0.5mg/kg/day prednisone equivalent within 7 days of enrollment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to vaccine agents
• Clinically significant uncontrolled illness
• 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

Other

• History (suspected or confirmed) of myocarditis or pericarditis
• Females only: Pregnant or breastfeeding
• 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

• 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)