Cytomegaloviral InfectionPhase 1NCT05589844
A Cytomegalovirus-Directed Vaccine (CMV-alphaDC1) for Preventing Cytomegalovirus Infection or Reactivation in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
A Phase 1 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Biospecimen Collection and CMV pp65 Peptide-loaded Alpha-type-1 Polarized Dendritic Cell Vaccine in people with Cytomegaloviral Infection and Hematopoietic and Lymphoid System Neoplasm, run by Roswell Park Cancer Institute at 1 site in United States.
Trial summary
This phase Ib trial evaluates the safety and most effective dose of a cytomegalovirus (CMV) pp65 peptide-loaded alpha-type-1 polarized dendritic cell (CMV-alphaDC1) vaccination in patients who are undergoing an allogeneic hematopoietic stem cell transplant. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cytomegaloviral Infection, Hematopoietic and Lymphoid System Neoplasm
- What is being tested?
- Allogeneic Hematopoietic Stem Cell Transplantation, Biospecimen Collection and CMV pp65 Peptide-loaded Alpha-type-1 Polarized Dendritic Cell Vaccine
- Type of treatment
- Vaccines, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2023to 16 Nov 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Recipient age >= 18 years of age
- The recipient is CMV seropositive
- The recipient is planned to receive an allogeneic peripheral blood stem cell graft
- The recipient is planned to receive fludarabine, melphalan, and total body irradiation for the transplant conditioning regimen
- The recipient is planned to receive micro-dose methotrexate, tacrolimus, and mycophenolate mofetil for acute graft versus host disease (GvHD) prophylaxis
- The recipient has an expected hematopoietic cell transplantation-comorbidity index (HCT-CI) score of 4 or less based upon the data available at the time of eligibility assessment
Show all 11Show fewer
- The recipient must understand the investigational nature of this study and has signed an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedures
- The donor is CMV seronegative or seropositive
- The donor is 8/8 human leukocyte antigen (HLA) (DR-B1, A, B, C) matched to the recipient
- The donor is willing and able to donate peripheral blood mononuclear cells in addition to peripheral blood stem cells
- The donor is willing to sign informed consent
Who cannot join
- The recipient is CMV seronegative
- The recipient is planned to receive T cell depletion in vivo (anti-thymocyte globulin [ATG], alemtuzumab, post-transplant cyclophosphamide) or ex vivo (alpha-beta T cell depleted or CD34+ selected grafts) as acute GvHD prophylaxis
- The graft source is cord blood or bone marrow
- The donor or recipient has HLA DRB1*0301 or DRB1*1501 alleles
- The recipient has a very high disease risk index (DRI) based upon the data available at the time of eligibility assessment
- The recipient has a medical, behavioral, or social condition which in the opinion of the investigators would preclude compliance with the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Roswell Park Cancer Institute
Buffalo, New York, 14263
About this study
Official title: A Phase 1b Safety and Immunogenicity Study of Cytomegalovirus (CMV) Directed Type 1 Polarized Dendritic Cell Vaccination (αDC1) After Allogeneic Hematopoietic Cell Transplantation (alloHCT) for Hematologic Malignancies
This phase Ib trial evaluates the safety and most effective dose of a cytomegalovirus (CMV) pp65 peptide-loaded alpha-type-1 polarized dendritic cell (CMV-alphaDC1) vaccination in patients who are undergoing an allogeneic hematopoietic stem cell transplant. CMV is an opportunistic infection that can occur or reactivate after allogeneic hematopoietic stem cell transplant as a result of immunosuppression. The CMV-alphaDC1 vaccine is made of white blood cells that have been exposed to molecules called cytokines, as well as CMV proteins. Introducing these dendritic cells to the patients immune system may activate an immune response to CMV, protecting against infection or reactivation.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the safety of cytomegalovirus (CMV) pp65 peptide loaded alpha-type 1 polarized dendritic cell (CMV-alphaDC1) vaccination after allogeneic hematopoietic cell transplantation (alloHCT).
II. Determine the immunogenicity of CMV-alphaDC1 vaccination after alloHCT.
SECONDARY OBJECTIVES:
- Evaluate the effect of CMV-alphaDC1 vaccination after alloHCT on late CMV reactivation.
II. Evaluate the effect of CMV-alphaDC1 vaccination after alloHCT on non-relapse mortality (NRM).
EXPLORATORY OBJECTIVES:
- Assess the effect of CMV-alphaDC1 vaccination on T cell subsets. II. Assess the effect of CMV-alphaDC1 vaccination on T cell receptor diversity.
OUTLINE:
On day 0, patients undergo standard of care hematopoietic stem cell infusion. Patients receive CMV-alphaDC1 vaccine intradermally on days 28, 42, 56, and 70.
After completion of study treatment, patients are followed up at days 84, 100, 180, and 365.
- Being tested
- Allogeneic Hematopoietic Stem Cell Transplantation, Biospecimen Collection, CMV pp65 Peptide-loaded Alpha-type-1 Polarized Dendritic Cell Vaccine
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC
Undergo standard of care allogeneic hematopoietic stem cell transplant
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Correlative studies
CMV pp65 Peptide-loaded Alpha-type-1 Polarized Dendritic Cell VaccineBiological
Also called CMV pp65 Peptide-loaded Alpha-type-1 Polarized DC Vaccine, Cytomegalovirus pp65 Peptide Loaded Alpha-type 1 Polarized Dendritic Cell Vaccine
Given intradermally
| Study group | Role | What they receive |
|---|---|---|
| Treatment (CMV-alphaDC1) | Experimental | Patients undergo standard of care allogeneic hematopoietic stem cell transplant on day 0 and receive CMV-alphaDC1 vaccine intradermally on days 28, 42, 56, and 70. Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Biospecimen Collection; Biological: CMV pp65 Peptide-loaded Alpha-type-1 Polarized Dendritic Cell Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose limiting toxicities
For each dose level of cytomegalovirus (CMV) pp65 peptide loaded alpha-type 1 polarized dendritic cell (CMV-alphaDC1) vaccination that is tested. Will be summarized by dose level using frequencies and relative frequencies.
Measured: Up to 2 years
Number of multifunctional CMV antigen specific T cells
The number of multifunctional CMV antigen specific T cells will be determined by flow cytometry before and after vaccination with CMV-alphaDC1. Assessed by the change in the number of CMV specific T cells before and after treatment, which is compared using a one-sided paired t-test. The number of CMV specific T cells will be summarized before and after treatment using the appropriate descriptive statistics, with the mean change estimated using a 90% confidence interval.
Measured: At days 28 (before vaccination), 42 (before vaccination), 56, 70, 84, 100, 180, 365
Number of CMV pp56 reactive T cells
The number of CMV pp65 reactive T cells will be determined by cytokine secretion (such as IFN-gamma) with ELISPOT before and after vaccination with CMV-alphaDC1. Assessed by the change in the number of CMV specific T cells before and after treatment, which is compared using a one-sided paired t-test. The number of CMV specific T cells will be summarized before and after treatment using the appropriate descriptive statistics, with the mean change estimated using a 90% confidence interval.
Measured: At days 28 (before vaccination), 42 (before vaccination), 56, 70, 84, 100, 180, 365
Secondary outcomes (2)
Incidence of late CMV reactivation after allogeneic hematopoietic stem cell transplant
Will be summarized by dose level using the appropriate descriptive statistics; with estimates of rates obtained by 95% Jeffrey's prior confidence intervals.
Measured: From day 85 to 365
Incidence of non-relapse mortality after allogeneic hematopoietic stem cell transplant
Will be summarized by dose level using the appropriate descriptive statistics; with estimates of rates obtained by 95% Jeffrey's prior confidence intervals.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2022
- Study startMar 2023 (estimated)
- Primary completion16 Nov 2024 (estimated)
- Study completion16 Nov 2025 (estimated)
Why it stopped: Study never approved
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cytomegaloviral InfectionStudies of the same condition, open and under way.
- More trials run by Roswell Park Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- George L Chen, Principal investigator, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05589844
- Sponsor's protocol ID
- I 1289721
- Other IDs
- NCI-2022-05780, I 1289721
- Status last verified
- Apr 2023
- First submitted
- 17 Oct 2022
- Last updated
- 27 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Safety and Immunogenicity Study of Cytomegalovirus (CMV) Directed Type 1 Polarized Dendritic Cell Vaccination (αDC1) After Allogeneic Hematopoietic Cell Transplantation (alloHCT) for Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT05589844
- Acronym / sponsor ID
- I 1289721
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study never approved
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Roswell Park Cancer InstituteUniversity, hospital or other
- Study start
- Mar 2023 (estimated)
- Primary completion
- 16 Nov 2024 (estimated)
- Study completion
- 16 Nov 2025 (estimated)
- First posted
- 21 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase Ib trial evaluates the safety and most effective dose of a cytomegalovirus (CMV) pp65 peptide-loaded alpha-type-1 polarized dendritic cell (CMV-alphaDC1) vaccination in patients who are undergoing an allogeneic hematopoietic stem cell transplant. CMV is an opportunistic infection that can occur or reactivate after allogeneic hematopoietic stem cell transplant as a result of immunosuppression. The CMV-alphaDC1 vaccine is made of white blood cells that have been exposed to molecules called cytokines, as well as CMV proteins. Introducing these dendritic cells to the patients immune system may activate an immune response to CMV, protecting against infection or reactivation.
Detailed description
PRIMARY OBJECTIVES:
- Determine the safety of cytomegalovirus (CMV) pp65 peptide loaded alpha-type 1 polarized dendritic cell (CMV-alphaDC1) vaccination after allogeneic hematopoietic cell transplantation (alloHCT).
II. Determine the immunogenicity of CMV-alphaDC1 vaccination after alloHCT.
SECONDARY OBJECTIVES:
- Evaluate the effect of CMV-alphaDC1 vaccination after alloHCT on late CMV reactivation.
II. Evaluate the effect of CMV-alphaDC1 vaccination after alloHCT on non-relapse mortality (NRM).
EXPLORATORY OBJECTIVES:
- Assess the effect of CMV-alphaDC1 vaccination on T cell subsets. II. Assess the effect of CMV-alphaDC1 vaccination on T cell receptor diversity.
OUTLINE:
On day 0, patients undergo standard of care hematopoietic stem cell infusion. Patients receive CMV-alphaDC1 vaccine intradermally on days 28, 42, 56, and 70.
After completion of study treatment, patients are followed up at days 84, 100, 180, and 365.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (CMV-alphaDC1) | Experimental | Procedure: Allogeneic Hematopoietic Stem Cell Transplantation, Procedure: Biospecimen Collection, Biological: CMV pp65 Peptide-loaded Alpha-type-1 Polarized Dendritic Cell VaccinePatients undergo standard of care allogeneic hematopoietic stem cell transplant on day 0 and receive CMV-alphaDC1 vaccine intradermally on days 28, 42, 56, and 70. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Recipient age >= 18 years of age
- The recipient is CMV seropositive
- The recipient is planned to receive an allogeneic peripheral blood stem cell graft
- The recipient is planned to receive fludarabine, melphalan, and total body irradiation for the transplant conditioning regimen
- The recipient is planned to receive micro-dose methotrexate, tacrolimus, and mycophenolate mofetil for acute graft versus host disease (GvHD) prophylaxis
Key exclusion criteria (6 listed)
- The recipient is CMV seronegative
- The recipient is planned to receive T cell depletion in vivo (anti-thymocyte globulin [ATG], alemtuzumab, post-transplant cyclophosphamide) or ex vivo (alpha-beta T cell depleted or CD34+ selected grafts) as acute GvHD prophylaxis
- The graft source is cord blood or bone marrow
- The donor or recipient has HLA DRB1*0301 or DRB1*1501 alleles
- The recipient has a very high disease risk index (DRI) based upon the data available at the time of eligibility assessment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Allogeneic Hematopoietic Stem Cell TransplantationAlso: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSCUndergo standard of care allogeneic hematopoietic stem cell transplant | Procedure or surgery | Treatment (CMV-alphaDC1) |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Specimen CollectionCorrelative studies | Procedure or surgery | Treatment (CMV-alphaDC1) |
| CMV pp65 Peptide-loaded Alpha-type-1 Polarized Dendritic Cell VaccineAlso: CMV pp65 Peptide-loaded Alpha-type-1 Polarized DC Vaccine, Cytomegalovirus pp65 Peptide Loaded Alpha-type 1 Polarized Dendritic Cell VaccineGiven intradermally | Biological | Treatment (CMV-alphaDC1) |
Primary outcome
Incidence of dose limiting toxicities
Time frame: Up to 2 years
For each dose level of cytomegalovirus (CMV) pp65 peptide loaded alpha-type 1 polarized dendritic cell (CMV-alphaDC1) vaccination that is tested. Will be summarized by dose level using frequencies and relative frequencies.
Number of multifunctional CMV antigen specific T cells
Time frame: At days 28 (before vaccination), 42 (before vaccination), 56, 70, 84, 100, 180, 365
The number of multifunctional CMV antigen specific T cells will be determined by flow cytometry before and after vaccination with CMV-alphaDC1. Assessed by the change in the number of CMV specific T cells before and after treatment, which is compared using a one-sided paired t-test. The number of CMV specific T cells will be summarized before and after treatment using the appropriate descriptive statistics, with the mean change estimated using a 90% confidence interval.
Number of CMV pp56 reactive T cells
Time frame: At days 28 (before vaccination), 42 (before vaccination), 56, 70, 84, 100, 180, 365
The number of CMV pp65 reactive T cells will be determined by cytokine secretion (such as IFN-gamma) with ELISPOT before and after vaccination with CMV-alphaDC1. Assessed by the change in the number of CMV specific T cells before and after treatment, which is compared using a one-sided paired t-test. The number of CMV specific T cells will be summarized before and after treatment using the appropriate descriptive statistics, with the mean change estimated using a 90% confidence interval.
2 secondary outcomes
Incidence of late CMV reactivation after allogeneic hematopoietic stem cell transplant
Time frame: From day 85 to 365
Incidence of non-relapse mortality after allogeneic hematopoietic stem cell transplant
Time frame: Up to 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
George L Chen principal investigator
Roswell Park Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Biospecimen Collection and CMV pp65 Peptide-loaded Alpha-type-1 Polarized Dendritic Cell Vaccine in people with Cytomegaloviral Infection and Hematopoietic and Lymphoid System Neoplasm, run by Roswell Park Cancer Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 27 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose limiting toxicities (time frame: Up to 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2023.