Clinical trial NCT04977024: SARS-CoV-2 Vaccine (GEO-CM04S1) Versus mRNA SARS-COV-2 Vaccine in Patients With Blood Cancer
Official title: A Phase 2 Randomized, Multi-center Study of GEO-CMO4S1 (SARS-CoV-2 Vaccine) Versus mRNA SARS-CoV-2 Vaccine in Patients Post Cellular Therapy for Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: COVID-19 Infection
Hematopoietic and Lymphoid System Neoplasm
Leukemia
Lymphoma
Plasma Cell Myeloma
Lead sponsor: GeoVax, Inc.
Sponsor class: INDUSTRY
First posted: 2021-07-26
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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 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 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

Primary outcomes:
measure: Biological response
timeFrame: At 28 days post the second vaccine injection
Secondary outcomes:
measure: Incidence of moderate adverse events (AEs)
timeFrame: Up to 365 days
measure: Incidence of unacceptable AEs
timeFrame: Up to 365 days
measure: Non-relapse mortality
timeFrame: Up to 365 days
measure: Incidence of graft-versus-host disease (GVHD)
timeFrame: Up to 365 days
measure: Incidence of Severe coronavirus disease 2019 (COVID-19)
timeFrame: Up to 365 days
measure: Th1 vs Th2 polarization
timeFrame: Up to 365 days
measure: Antigen specific T cell responses to the COH04S1 vaccine
timeFrame: Up to 365 days
measure: Percentages of activated/cycling and memory phenotype markers on the surface of antigen-specific T cells
timeFrame: Up to 365 days
measure: Humoral immunity
timeFrame: Up to 365 days
measure: Neutralizing antibodies
timeFrame: Up to 365 days
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Worcester
country: United States
facility: U Mass Chan Medical School
state: Massachusetts
city: Stony Brook
country: United States
facility: SUNY-Stony Brook
state: New York
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest Baptist
state: North Carolina
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
Study officials:
affiliation: GeoVax, Inc.
name: Chief Medical Officer
role: PRINCIPAL_INVESTIGATOR
References: