Official Title
A Multi-Center, Observer-Blinded, EUA Vaccine-Controlled, Randomized Phase II Study to Evaluate the Biological Activity of COH04S1 (SARS-CoV-2 Vaccine) Compared to EUA SARS-CoV-2 Vaccines in Hematology Patients Who Have Received Cellular Therapy (HCT or CAR-T)
Brief Summary

This phase II trial studies the immune response to COH04S1 compared to Emergency Use Authorization (EUA) SARS-COV-2 vaccine in patients with blood cancer who have received stem cell transplant or cellular therapy. COH04S1 belongs to a category called modified vaccinia Ankara (MVA) vaccines, created from a new version of MVA, called synthetic MVA. COH04S1 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 COH04S1 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 EUA SARS-CoV-2 vaccine.

Detailed Description

PRIMARY OBJECTIVE:



I. Evaluate the biological activity and the role of timing of 2 injections of COH04S1 vaccine

administered at 2.5x10e8 PFU/dose compared to EUA vaccine.



SECONDARY OBJECTIVES:



I. Assess safety of COH04S1 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 COH04S1 intramuscularly (IM) in the upper arm on days 0

and 28.



ARM II : Patients receive one dose of EUA 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.

Not yet recruiting
Covid-19 Infection
Hematopoietic and Lymphoid System Neoplasm
Leukemia
Lymphoma
Plasma Cell Myeloma

Biological: COVID-19 Vaccine
Receive EUA SARS-CoV-2 vaccine IM
Arm II (EUA SARS-CoV-2 vaccine)

Other: Diagnostic Laboratory Biomarker Analysis
Correlative studies
Arm I (COH04S1)
Arm II (EUA SARS-CoV-2 vaccine)

Biological: Synthetic MVA-based SARS-CoV-2 Vaccine COH04S1
Given IM
Arm I (COH04S1)
Other Name: COH04S1
Other Name: SARS-CoV-2 Vaccine COH04S1
Other Name: sMVA-based SARS-CoV-2 Vaccine COH04S1

Eligibility Criteria

Inclusion Criteria: - Documented informed consent of the participant - Age >=18 years - Eastern Cooperative Oncology Group (ECOG) =< 2 - 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) - 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: - Patients who have received second allogeneic HCT are not eligible (patients who have undergone a previous autologous HCT are eligible - Systemic corticosteroids required for chronic conditions at doses > 0.5mg/kg/day prednisone equivalent - Patients on maintenance therapies (e.g. rituximab, Bruton tyrosine kinase inhibitors, Janus kinase inhibitors), who may have significantly attenuated response to vaccination - Subjects using investigational or licensed agents that may prevent or treat SARS-CoV-2 are excluded such as any previous SARS-CoV-2 vaccine - Subjects who have had 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 - 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

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years
Countries
United States
Locations

City of Hope Medical Center
Duarte, California, 91010

Investigator: Sanjeet S. Dadwal
Contact: 626-218-8202
sdadwal@coh.org

Investigator: Sanjeet S. Dadwal

Sanjeet S Dadwal
Principal Investigator
City of Hope Medical Center

City of Hope Medical Center
National Cancer Institute (NCI)
NCT Number
MeSH Terms
Multiple Myeloma
Neoplasms, Plasma Cell
Vaccines