Vaccine Booster GEO-CM04S1 for Chronic Lymphocytic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Systemic corticosteroids

Disqualifiers: Current SARS CoV-2, HCT, CAR T, 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: 2

Duration: 12 weeks

80 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids at high doses or have had certain intensive therapies recently, you may not be eligible. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment GEO-CM04S1 for Chronic Lymphocytic Leukemia?

Research shows that patients with chronic lymphocytic leukemia (CLL) often have a poor immune response to standard COVID-19 vaccines, but additional booster doses can enhance immune responses, including T-cell activation, which is important for long-term protection. This suggests that booster vaccines, like GEO-CM04S1, could potentially improve immune responses in CLL patients. ^{1 2 3 4 5}

Is the COH04S1 vaccine safe for humans?

The COH04S1 vaccine has been tested in cancer patients and healthy adults, showing strong immune responses and no major safety concerns reported in the studies. It was well-tolerated in these groups, suggesting it is generally safe for humans. ^{5 6 7 8 9}

How is the treatment COH04S1 different from other treatments for chronic lymphocytic leukemia?

The COH04S1 vaccine is unique because it is a synthetic vaccine based on modified vaccinia Ankara (MVA) that targets both the spike and nucleocapsid proteins of the SARS-CoV-2 virus, potentially offering broader immune protection. This approach is different from traditional mRNA vaccines, which typically target only the spike protein, and it has shown promising immune responses in immunocompromised patients, such as those who have undergone hematopoietic cell transplantation. ^{2 4 5 6 9}

What is the purpose of this trial?

This trial compares a new COVID-19 vaccine, GEO-CM04S1, with the standard vaccine in patients with chronic lymphocytic leukemia (CLL). The new vaccine aims to boost the immune system more effectively in these patients. It works by helping the body produce more infection-fighting cells.

Research Team

Alexey V. Danilov

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

Adults diagnosed with chronic lymphocytic leukemia (CLL) who have had at least two Pfizer or Moderna COVID-19 vaccines over three months ago can join. They should be in good health otherwise, not pregnant, and willing to use birth control. People with recent intensive cancer treatments, certain allergies, a history of heart inflammation, or those on high-dose steroids cannot participate.

Inclusion Criteria

My bilirubin levels are normal or slightly above, unless I have Gilbert's disease.

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 vaccine injection

Your platelet count needs to be at least 50,000 per cubic millimeter within 14 days before starting the treatment.

Exclusion Criteria

I have had pericarditis or myocarditis in the past.

I have not received a poxvirus vaccine in the last year.

I have an infection that isn't getting better with treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the GEO-CM04S1 vaccine or mRNA vaccine on days 0 and 84

12 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular monitoring throughout the year

Treatment Details

Interventions

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

Trial Overview The trial is testing the GEO-CM04S1 vaccine booster against standard COVID-19 vaccines for CLL patients. The new vaccine uses a modified virus that might better stimulate immune cells even when the immune system is weakened by CLL.

Participant Groups

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

Patients receive GEO-CM04S1 vaccine IM on days 0 and 84 on study. Patients undergo blood sample collections throughout the study and are monitored for 1 year.

Group II: Arm II (mRNA Covid-19 Vaccine) Active Control 2 Interventions

Patients receive mRNA vaccine injection IM on days 0 and 84 on study. Patients undergo blood sample collections throughout the study and are monitored for 1 year.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a small study of two chronic lymphocytic leukemia (CLL) patients, a third heterologous vaccine dose after an initial two-dose mRNA series showed promising results, with one patient developing specific immune responses including antibodies and memory B-cells.

Both patients exhibited a spike-specific CD8 T-cell response, indicating that a third dose can enhance immune responses in CLL patients who initially did not respond to the mRNA vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity of Pfizer mRNA COVID-19 Vaccination Followed by J&J Adenovirus COVID-19 Vaccination in Two Patients with Chronic Lymphocytic Leukemia. Lyski, ZL., Kim, MS., Xthona Lee, D., 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 study involving two Chronic Lymphocytic Leukemia (CLL) patients who did not respond to the initial mRNA COVID-19 vaccine series, one patient successfully developed an immune response after receiving a heterologous third vaccination with Ad26.COV2.S, indicating potential benefits of this approach for similar patients.

The findings suggest that while one patient showed a robust immune response with specific antibodies and T-cells after the third dose, the other patient did not, highlighting the variability in immune responses among CLL patients and the need for tailored vaccination strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity of Pfizer mRNA COVID-19 vaccination followed by J&J adenovirus COVID-19 vaccination in two CLL patients. Lyski, ZL., Kim, S., Lee, DX., et al.[2022]

Patients with chronic lymphocytic leukemia (CLL) and myeloid dysplastic syndrome (MDS) showed a strong and persistent CD8+ T cell response to the BNT162b2 COVID-19 vaccine, with memory T cells detectable up to six months post-vaccination.

A second booster dose significantly enhanced the frequency of antigen-specific CD8+ T cells and broadened the range of T cell specificities, suggesting that booster vaccinations could provide important long-term protection against COVID-19 in these high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three doses of BNT162b2 COVID-19 mRNA vaccine establish long-lasting CD8+ T cell immunity in CLL and MDS patients. Hernandez, SPA., Hersby, DS., Munk, KK., 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 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]

The COH04S1 vaccine, a synthetic multiantigen MVA-based COVID-19 vaccine, successfully stimulated strong immune responses, including both humoral and cellular immunity, in a phase 1 trial with healthy adults.

Both COH04S1 and the mRNA vaccine BNT162b2 maintained robust T cell immunity for at least six months, providing a critical second line of defense against SARS-CoV-2 variants, despite reduced neutralizing antibody activity against variants like Delta and Omicron.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine-induced spike- and nucleocapsid-specific cellular responses maintain potent cross-reactivity to SARS-CoV-2 Delta and Omicron variants. Chiuppesi, F., Zaia, JA., Faircloth, K., et al.[2022]

The synthetic SARS-CoV-2 spike glycoprotein-coated lipid vesicles (S-LVs) induced high levels of neutralizing antibodies and T helper cell responses in cynomolgus macaques, demonstrating strong immunogenicity against multiple variants of the virus.

Vaccinated macaques achieved complete protection from SARS-CoV-2 infection, indicating that the S-LV vaccine candidate not only elicits a robust immune response but also provides sterilizing immunity, making it a promising candidate for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection. Sulbaran, G., Maisonnasse, P., Amen, A., et al.[2022]

In a study of 16 patients with chronic myeloid leukaemia (CML), 87.5% showed a strong immune response with neutralizing antibodies after a single dose of the Pfizer-BioNTech SARS-CoV-2 vaccine, indicating effective immunogenicity in this vulnerable group.

The majority of patients also demonstrated a robust T-cell response, with 80% exhibiting polyfunctional T-cell activity, suggesting that CML patients can mount a significant immune defense against SARS-CoV-2 following vaccination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single dose of BNT162b2 mRNA vaccine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induces neutralising antibody and polyfunctional T-cell responses in patients with chronic myeloid leukaemia. Harrington, P., Doores, KJ., Radia, D., et al.[2023]

References

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

Immunogenicity of Pfizer mRNA COVID-19 Vaccination Followed by J&J Adenovirus COVID-19 Vaccination in Two Patients with Chronic Lymphocytic Leukemia. [2022]

2. 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]

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

Immunogenicity of Pfizer mRNA COVID-19 vaccination followed by J&J adenovirus COVID-19 vaccination in two CLL patients. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Three doses of BNT162b2 COVID-19 mRNA vaccine establish long-lasting CD8+ T cell immunity in CLL and MDS patients. [2023]

5. Greece pubmed.ncbi.nlm.nih.gov

The Effectiveness of Bivalent mRNA Omicron Containing Booster Vaccines Among Patients With Hematological Neoplasms. [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. United States pubmed.ncbi.nlm.nih.gov

Vaccine-induced spike- and nucleocapsid-specific cellular responses maintain potent cross-reactivity to SARS-CoV-2 Delta and Omicron variants. [2022]

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

Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Single dose of BNT162b2 mRNA vaccine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induces neutralising antibody and polyfunctional T-cell responses in patients with chronic myeloid leukaemia. [2023]