Vaccine Booster GEO-CM04S1 for Chronic Lymphocytic Leukemia
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: City of Hope Medical Center
Must not be taking: Systemic corticosteroids
Disqualifiers: Current SARS CoV-2, HCT, CAR T, others
No Placebo Group
Prior Safety Data
Trial Summary
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.
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.
12345Is 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.
56789How 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.
24569Eligibility 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.
+12 more
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.
+11 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm I (GEO-CM04S1)Experimental Treatment2 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 Control2 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
City of Hope Medical CenterDuarte, CA
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Who Is Running the Clinical Trial?
City of Hope Medical CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Immunogenicity of Pfizer mRNA COVID-19 Vaccination Followed by J&J Adenovirus COVID-19 Vaccination in Two Patients with Chronic Lymphocytic Leukemia. [2022]Individuals with chronic lymphocytic leukemia (CLL) have significant immune disfunction, often further disrupted by treatment. While currently available COVID-19 vaccinations are highly effective in immunocompetent individuals, they are often poorly immunogenic in CLL patients. It is important to understand the role a heterologous boost would have in patients who did not respond to the initial two-dose mRNA vaccine series. SARS-CoV-2 specific immune responses, including antibodies and memory B-cells, CD4 and CD8 T-cells were assessed prior to vaccination, as well as postinitial vaccination series and post-third dose in two subjects. One subject seroconverted, had RBD-specific memory B-cells and spike-specific CD4 T-cells while the other did not. Both subjects had a spike-specific CD8 T-cell response after the original mRNA vaccination series that was further boosted after the third dose or remained stable. The results of this study, however small, are especially promising to CLL individuals who did not seroconvert following the initial mRNA vaccination series.
Serological and cellular response to mRNA-SARS-CoV2 vaccine in patients with hematological lymphoid malignancies: Results of the study "Cervax". [2023]messenger RNA (mRNA)-Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccines such as BNT162b2 became available in late 2020, but hematological malignancy patients (HM pts) were not evaluated in initial registration trials. We hereby report the results of a prospective, unicentric, observational study Response to COVID-19 Vaccination in hEmatological malignancies (CERVAX) developed to assess the postvaccine serological and T-cell-mediated response in a cohort of SARS-CoV2-negative HM pts vaccinated with BNT162b2. Patients with lymphomas [non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL)], chronic lymphocytic leukemia (CLL), and multiple myeloma (MM); off-therapy for at least 3 months; in a watch-and-wait program; or in treatment with ibrutinib, venetoclax, and lenalidomide were included. Different time points were considered to assess the serological response to the vaccine: before the second dose (T1), at 3-6-12 months after the first dose (T2-3-4, respectively). Since March 2021, 39 pts have been enrolled: 15 (38%) NHL, 12 (31%) CLL, and 12 (31%) MM. There were 13 of the 39 pts (33%) seroconverted at T1; an increase of the serological response was registered after the second dose (T2) (22/39 pts, 56%) and maintained after 6 months (22/39 pts, 56%) and 12 months (24/39 pts, 61%) from the first dose (T3-T4, respectively). Non-serological responders at T4 were 7/39 (18%): 0/15 NHL, 1/12 MM (8%), and 6/12 CLL (50%). All of them were on therapy (one lenalidomide, three ibrutinib, and three venetoclax). SARS-CoV2-reactive T-cell analysis (interferon gamma release assays) was available since June 2022 and was evaluated at 12 months (T4) from the first dose of vaccine in 31/39 pts (79%). T-cell-mediated-responders were 17/31 (55%): most of them were NHL and MM (47%, 41% and 12% for NHL, MM, and CLL, respectively). Both serological and T-cell non-responders were represented by pts on active therapy (venetoclax/ibrutinib). During the period of observation, eight (20.5%) pts developed mild SARS-CoV2 infection; no coronavirus disease 19 (COVID-19)-related deaths or hospitalizations were registered. In conclusion, in our cohort of lymphoproliferative pts receiving BNT162b2, CLL diagnosis and venetoclax/ibrutinib seem to be related with a lower humoral or T-mediated response. Nevertheless, the efficacy of mRNA vaccine in HM pts and the importance to continue the vaccine program even in non-responders after the first dose are supported in our study by demonstrating that a humoral and T-cell-mediated seroconversion should be observed even in the subsets of heavily immunocompromised pts.
Immunogenicity of Pfizer mRNA COVID-19 vaccination followed by J&J adenovirus COVID-19 vaccination in two CLL patients. [2022]Individuals with Chronic Lymphocytic Leukemia have significant immune disfunction, often further disrupted by treatment. While currently available COVID-19 vaccinations are highly effective in immunocompetent individuals, they are often poorly immunogenic in CLL patients. It is important to understand the role heterologous boost would have in patients who did not respond to the recommended two-dose mRNA vaccine series with a SARS-CoV-2 specific immune response.
Three doses of BNT162b2 COVID-19 mRNA vaccine establish long-lasting CD8+ T cell immunity in CLL and MDS patients. [2023]Patients with hematological malignancies are prioritized for COVID-19 vaccine due to their high risk for severe SARS-CoV-2 infection-related disease and mortality. To understand T cell immunity, its long-term persistence, and its correlation with antibody response, we evaluated the BNT162b2 COVID-19 mRNA vaccine-specific immune response in chronic lymphocytic leukemia (CLL) and myeloid dysplastic syndrome (MDS) patients. Longitudinal analysis of CD8+ T cells using DNA-barcoded peptide-MHC multimers covering the full SARS-CoV-2 Spike-protein (415 peptides) showed vaccine-specific T cell activation and persistence of memory T cells up to six months post-vaccination. Surprisingly, a higher frequency of vaccine-induced antigen-specific CD8+ T cells was observed in the patient group compared to a healthy donor group. Furthermore, and importantly, immunization with the second booster dose significantly increased the frequency of antigen-specific CD8+ T cells as well as the total number of T cell specificities. Altogether 59 BNT162b2 mRNA vaccine-derived immunogenic responses were identified, of which 23 established long-term CD8+ T cell memory response with a strong immunodominance for NYNYLYRLF (HLA-A24:02) and YLQPRTFLL (HLA-A02:01) epitopes. In summary, we mapped the vaccine-induced antigen-specific CD8+ T cells and showed a booster-specific activation and enrichment of memory T cells that could be important for long-term disease protection in this patient group.
The Effectiveness of Bivalent mRNA Omicron Containing Booster Vaccines Among Patients With Hematological Neoplasms. [2023]Last year was characterized by the appearance of novel SARS-CoV-2 virus variants, mainly the omicron sub-lineages BA.2.12.1, BA.4, and BA.5, which have confirmed resistance to the acquired immune response developed following first-generation mRNA vaccines. Given the ability to use mRNA technology to respond quickly to variant strains, novel bivalent vaccines against novel omicron variants were generated. In the current work, we evaluated the efficacy and safety of novel bivalent mRNA Omicron-containing booster vaccines among patients with hematological neoplasms, including both lymphoproliferative and myeloid malignancies.
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]Hematopoietic cell transplantation (HCT) and chimeric antigen receptor (CAR)-T cell patients are immunocompromised, remain at high risk following SARS-CoV-2 infection, and are less likely than immunocompetent individuals to respond to vaccination. As part of the safety lead-in portion of a phase 2 clinical trial in patients post HCT/CAR-T for hematological malignancies (HM), we tested the immunogenicity of the synthetic modified vaccinia Ankara-based COVID-19 vaccine COH04S1 co-expressing spike (S) and nucleocapsid (N) antigens. Thirteen patients were vaccinated 3-12 months post HCT/CAR-T with two to four doses of COH04S1. SARS-CoV-2 antigen-specific humoral and cellular immune responses, including neutralizing antibodies to ancestral virus and variants of concern (VOC), were measured up to six months post vaccination and compared to immune responses in historical cohorts of naïve healthy volunteers (HV) vaccinated with COH04S1 and naïve healthcare workers (HCW) vaccinated with the FDA-approved mRNA vaccine Comirnaty® (Pfizer, New York, NY, USA). After one or two COH04S1 vaccine doses, HCT/CAR-T recipients showed a significant increase in S- and N-specific binding antibody titers and neutralizing antibodies with potent activity against SARS-CoV-2 ancestral virus and VOC, including the highly immune evasive Omicron XBB.1.5 variant. Furthermore, vaccination with COH04S1 resulted in a significant increase in S- and N-specific T cells, predominantly CD4+ T lymphocytes. Elevated S- and N-specific immune responses continued to persist at six months post vaccination. Furthermore, both humoral and cellular immune responses in COH04S1-vaccinated HCT/CAR-T patients were superior or comparable to those measured in COH04S1-vaccinated HV or Comirnaty®-vaccinated HCW. These results demonstrate robust stimulation of SARS-CoV-2 S- and N-specific immune responses including cross-reactive neutralizing antibodies by COH04S1 in HM patients post HCT/CAR-T, supporting further testing of COH04S1 in immunocompromised populations.
Vaccine-induced spike- and nucleocapsid-specific cellular responses maintain potent cross-reactivity to SARS-CoV-2 Delta and Omicron variants. [2022]Cell-mediated immunity may contribute to providing protection against SARS-CoV-2 and its variants of concern (VOC). We developed COH04S1, a synthetic multiantigen modified vaccinia Ankara (MVA)-based COVID-19 vaccine that stimulated potent spike (S) and nucleocapsid (N) antigen-specific humoral and cellular immunity in a phase 1 clinical trial in healthy adults. Here, we show that individuals vaccinated with COH04S1 or mRNA vaccine BNT162b2 maintain robust cross-reactive cellular immunity for six or more months post-vaccination. Although neutralizing antibodies induced in COH04S1- and BNT162b2-vaccinees showed reduced activity against Delta and Omicron variants compared to ancestral SARS-CoV-2, S-specific T cells elicited in both COH04S1- and BNT162b2-vaccinees and N-specific T cells elicited in COH04S1-vaccinees demonstrated potent and equivalent cross-reactivity against ancestral SARS-CoV-2 and the major VOC. These results suggest that vaccine-induced T cells to S and N antigens may constitute a critical second line of defense to provide long-term protection against SARS-CoV-2 VOC.
Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection. [2022]The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused an ongoing global health crisis. Here, we present as a vaccine candidate synthetic SARS-CoV-2 spike (S) glycoprotein-coated lipid vesicles that resemble virus-like particles. Soluble S glycoprotein trimer stabilization by formaldehyde cross-linking introduces two major inter-protomer cross-links that keep all receptor-binding domains in the "down" conformation. Immunization of cynomolgus macaques with S coated onto lipid vesicles (S-LVs) induces high antibody titers with potent neutralizing activity against the vaccine strain, Alpha, Beta, and Gamma variants as well as T helper (Th)1 CD4+-biased T cell responses. Although anti-receptor-binding domain (RBD)-specific antibody responses are initially predominant, the third immunization boosts significant non-RBD antibody titers. Challenging vaccinated animals with SARS-CoV-2 shows a complete protection through sterilizing immunity, which correlates with the presence of nasopharyngeal anti-S immunoglobulin G (IgG) and IgA titers. Thus, the S-LV approach is an efficient and safe vaccine candidate based on a proven classical approach for further development and clinical testing.
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]Patients receiving targeted cancer treatments such as tyrosine kinase inhibitors (TKIs) have been classified in the clinically extremely vulnerable group to develop severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), including patients with chronic myeloid leukaemia (CML) taking TKIs. In addition, concerns that immunocompromised individuals with solid and haematological malignancies may not mount an adequate immune response to a single dose of SARS-CoV-2 BNT162b2 (Pfizer-BioNTech) vaccine have been raised. In the present study, we evaluated humoral and cellular immune responses after a first injection of BNT162b2 vaccine in 16 patients with CML. Seroconversion and cellular immune response before and after vaccination were assessed. By day 21 after vaccination, anti-Spike immunoglobulin G was detected in 14/16 (87·5%) of the patients with CML and all developed a neutralising antibody response [serum dilution that inhibits 50% infection (ID50 ) >50], including medium (ID50 of 200-500) or high (ID50 of 501-2000) neutralising antibodies titres in nine of the 16 (56·25%) patients. T-cell response was seen in 14/15 (93·3%) evaluable patients, with polyfunctional responses seen in 12/15 (80%) patients (polyfunctional CD4+ response nine of 15, polyfunctional CD8+ T-cell response nine of 15). These data demonstrate the immunogenicity of a single dose of SARS-CoV-2 BNT162b2 vaccine in most patients with CML, with both neutralising antibodies and polyfunctional T-cell responses seen in contrast to patients with solid tumour or lymphoid haematological malignancies.