New Vaccine COH04S1 vs. mRNA COVID-19 Vaccine for Blood Cancer

Recruiting at 5 trial locations

Overseen By Director Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Corticosteroids, Rituximab, others

Disqualifiers: Myocarditis, Pericarditis, uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 4 weeks

240 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those on certain therapies like systemic corticosteroids at high doses, therapies causing T-cell or B-cell depletion, and some maintenance therapies within 30 days of enrollment. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment COH04S1 for blood cancer patients?

The research indicates that COVID-19 vaccines, including mRNA vaccines, have shown effectiveness in generating an immune response in patients with blood cancers, although the response may be lower compared to healthy individuals. This suggests that COH04S1, as a SARS-CoV-2 vaccine, could potentially offer some level of protection for these patients. ^{1 2 3 4 5}

Is the COH04S1 vaccine safe for humans?

In a study involving cancer patients who had undergone specific treatments, the COH04S1 vaccine was tested and showed strong immune responses without any significant safety concerns reported. This suggests it is generally safe for use in humans, including those with weakened immune systems. ^{1 2 3 4 6}

How is the COH04S1 vaccine different from other COVID-19 vaccines for blood cancer patients?

The COH04S1 vaccine is unique because it is a synthetic vaccine based on modified vaccinia Ankara (MVA) that targets both the spike (S) and nucleocapsid (N) proteins of the virus, which helps stimulate strong immune responses in blood cancer patients who are often immunocompromised. This vaccine has shown to produce robust antibody and T-cell responses, even against variants like Omicron, which is particularly beneficial for patients who may not respond well to traditional mRNA vaccines. ^{1 2 6 7 8}

Research Team

Chief Medical Officer

Principal Investigator

GeoVax, Inc.

Eligibility Criteria

Adults with blood cancers who've had stem cell transplants or CAR T-cell therapy at least 3 months ago. They must be in good health, not pregnant, agree to birth control, and have normal organ function tests. Those who got a COVID-19 vaccine after their therapy or have certain medical treatments or conditions are excluded.

Inclusion Criteria

Documented informed consent of the participant

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

I am capable of becoming pregnant or fathering a child.

Exclusion Criteria

Anyone considered to be in a vulnerable population as defined in 45 CFR §46.111 (a)(3) and 45 CFR §46, Subparts B-D

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)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two doses of either GEO-CM04S1 or SOC mRNA SARS-CoV-2 vaccine on days 0 and 28

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits on days 7, 90, 120, 180, and 365

365 days

5 visits (in-person)

Treatment Details

Interventions

• COVID-19 Vaccine
• Synthetic MVA-based SARS-CoV-2 Vaccine COH04S1

Trial Overview The trial is testing GEO-CM04S1, a synthetic MVA-based SARS-CoV-2 vaccine against standard mRNA vaccines in blood cancer patients post-transplant or cellular therapy. It aims to see if GEO-CM04S1 offers better protection from COVID-19.

Participant Groups

Group I: Arm II (SOC mRNA SARS-CoV-2 vaccine) Experimental Treatment 2 Interventions

Patients receive one dose of SOC mRNA SARS-CoV-2 vaccine IM in the upper arm on days 0 and 28.

Group II: Arm I (GEO-CM04S1) Experimental Treatment 2 Interventions

Patients receive one dose of GEO-CM04S1 IM in the upper arm on days 0 and 28.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

GeoVax, Inc.

Lead Sponsor

Trials

6

Recruited

440+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a systematic review of 49 studies involving 11,086 patients with hematological malignancies, the overall antibody response to COVID-19 vaccination was 64%, significantly lower than the 96% response in solid cancer patients and 98% in healthy controls, highlighting the need for tailored vaccination strategies for these patients.

Specific hematological conditions showed varying responses, with chronic lymphocytic leukemia patients having the lowest response at 50%, while those with Hodgkin lymphoma had a higher response at 91%. Factors such as being in remission and prior COVID-19 infection were associated with better vaccine responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody response after vaccination against SARS-CoV-2 in adults with hematological malignancies: a systematic review and meta-analysis. Gagelmann, N., Passamonti, F., Wolschke, C., et al.[2023]

The bivalent mRNA Omicron-containing booster vaccine significantly reduced the risk of COVID-19-related hospitalization among patients with hematological neoplasms, with only 2.9% of vaccinated patients requiring hospitalization compared to 10.4% in the non-vaccinated group, indicating an 89% relative risk reduction.

The vaccine demonstrated an acceptable safety profile, as no significant increase in ischemic stroke rates was observed among recipients, suggesting it is a safe option for this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effectiveness of Bivalent mRNA Omicron Containing Booster Vaccines Among Patients With Hematological Neoplasms. Tadmor, T., Melamed, G., Alapi, H., et al.[2023]

In a systematic review of 49 studies involving 11,086 patients with hematological malignancies, the overall antibody response to COVID-19 vaccination was 64%, significantly lower than the 96% response in solid cancer patients and 98% in healthy controls, highlighting the need for tailored vaccination strategies for these patients.

Specific hematological conditions showed varying responses, with chronic lymphocytic leukemia patients having the lowest response at 50%, while those in remission or with prior COVID-19 had significantly higher responses, indicating that treatment status and history can greatly influence vaccine efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody response after vaccination against SARS-CoV-2 in adults with hematological malignancies: a systematic review and meta-analysis. Wang, X., Sima, L.[2022]

Patients with hematological malignancies show limited immune response to COVID-19 vaccination, with seroconversion rates varying significantly (38.1-99.1%) depending on the type of cancer, particularly lower in those with chronic lymphocytic leukemia and those receiving B-cell depleting treatments.

Despite low rates of SARS-CoV-2 infection and severe outcomes (e.g., hospitalization and death), the impaired immune response highlights the need for new strategies to protect these patients, as current vaccine regimens may not provide adequate protection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness, immunogenicity, and safety of COVID-19 vaccines for individuals with hematological malignancies: a systematic review. Piechotta, V., Mellinghoff, SC., Hirsch, C., et al.[2022]

In a study of 39 patients with hematological malignancies vaccinated with the BNT162b2 mRNA COVID-19 vaccine, 61% showed a serological response 12 months after the first dose, indicating that the vaccine can elicit an immune response even in immunocompromised individuals.

Patients with chronic lymphocytic leukemia (CLL) and those on therapies like venetoclax or ibrutinib had lower rates of immune response, highlighting the need for continued vaccination efforts in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serological and cellular response to mRNA-SARS-CoV2 vaccine in patients with hematological lymphoid malignancies: Results of the study "Cervax". Mohamed, S., Lucchini, E., Sirianni, F., et al.[2023]

In a phase 2 clinical trial, the COH04S1 COVID-19 vaccine demonstrated strong immune responses in 13 patients post-hematopoietic cell transplantation (HCT) or CAR-T therapy, showing significant increases in antibodies and T cells specific to SARS-CoV-2 antigens.

The immune responses in these immunocompromised patients were comparable or superior to those seen in healthy volunteers vaccinated with COH04S1 and healthcare workers vaccinated with the FDA-approved mRNA vaccine, indicating that COH04S1 may be an effective option for protecting this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stimulation of Potent Humoral and Cellular Immunity via Synthetic Dual-Antigen MVA-Based COVID-19 Vaccine COH04S1 in Cancer Patients Post Hematopoietic Cell Transplantation and Cellular Therapy. Chiuppesi, F., Ortega-Francisco, S., Gutierrez, MA., et al.[2023]

A fourth mRNA COVID-19 vaccination significantly increased S1 IgG antibody concentrations in patients with haematological malignancies, although these levels remained lower than those in healthy individuals after their first booster vaccination.

19% of patients did not achieve seroconversion even after four vaccinations, but those who were vaccinated during B cell recovery showed improved antibody responses, suggesting that timing of vaccination relative to B cell status may enhance the quality of immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study. Hofsink, Q., Haggenburg, S., Lissenberg-Witte, BI., et al.[2023]

In a study of 585 cancer patients vaccinated with either BNT162b2 or AZD1222, seroconversion rates were 85% for those with solid tumors and only 59% for those with hematological malignancies, indicating a significant difference in immune response based on cancer type.

Patients with hematological malignancies had lower neutralizing antibody titers against SARS-CoV-2 variants compared to those with solid tumors, and prior COVID-19 infection improved antibody responses, highlighting the need for tailored vaccination strategies in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: The CAPTURE study. Fendler, A., Shepherd, STC., Au, L., et al.[2022]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Antibody response after vaccination against SARS-CoV-2 in adults with hematological malignancies: a systematic review and meta-analysis. [2023]

2. Greece pubmed.ncbi.nlm.nih.gov

The Effectiveness of Bivalent mRNA Omicron Containing Booster Vaccines Among Patients With Hematological Neoplasms. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Antibody response after vaccination against SARS-CoV-2 in adults with hematological malignancies: a systematic review and meta-analysis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Effectiveness, immunogenicity, and safety of COVID-19 vaccines for individuals with hematological malignancies: a systematic review. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Serological and cellular response to mRNA-SARS-CoV2 vaccine in patients with hematological lymphoid malignancies: Results of the study "Cervax". [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Stimulation of Potent Humoral and Cellular Immunity via Synthetic Dual-Antigen MVA-Based COVID-19 Vaccine COH04S1 in Cancer Patients Post Hematopoietic Cell Transplantation and Cellular Therapy. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: The CAPTURE study. [2022]