Overview
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.
Description
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
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 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 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