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A Cytomegalovirus-Directed Vaccine (CMV-alphaDC1) for Preventing Cytomegalovirus Infection or Reactivation in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Primary Purpose

Cytomegaloviral Infection, Hematopoietic and Lymphoid System Neoplasm

Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Allogeneic Hematopoietic Stem Cell Transplantation
Biospecimen Collection
CMV pp65 Peptide-loaded Alpha-type-1 Polarized Dendritic Cell Vaccine
Sponsored by
Roswell Park Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Cytomegaloviral Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • Roswell Park Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (CMV-alphaDC1)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
October 17, 2022
Last Updated
April 25, 2023
Sponsor
Roswell Park Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT05589844
Brief Title
A Cytomegalovirus-Directed Vaccine (CMV-alphaDC1) for Preventing Cytomegalovirus Infection or Reactivation in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Withdrawn
Why Stopped
Study never approved
Study Start Date
March 2023 (Anticipated)
Primary Completion Date
November 16, 2024 (Anticipated)
Study Completion Date
November 16, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Roswell Park Cancer Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief 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. 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: I. 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: I. 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: I. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cytomegaloviral Infection, Hematopoietic and Lymphoid System Neoplasm

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (CMV-alphaDC1)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Allogeneic Hematopoietic Stem Cell Transplantation
Other Intervention Name(s)
Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic
Intervention Description
Undergo standard of care allogeneic hematopoietic stem cell transplant
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection, Biospecimen Collected, Specimen Collection
Intervention Description
Correlative studies
Intervention Type
Biological
Intervention Name(s)
CMV pp65 Peptide-loaded Alpha-type-1 Polarized Dendritic Cell Vaccine
Other Intervention Name(s)
CMV pp65 Peptide-loaded Alpha-type-1 Polarized DC Vaccine, Cytomegalovirus pp65 Peptide Loaded Alpha-type 1 Polarized Dendritic Cell Vaccine
Intervention Description
Given intradermally
Primary Outcome Measure Information:
Title
Incidence of dose limiting toxicities
Description
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.
Time Frame
Up to 2 years
Title
Number of multifunctional CMV antigen specific T cells
Description
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.
Time Frame
At days 28 (before vaccination), 42 (before vaccination), 56, 70, 84, 100, 180, 365
Title
Number of CMV pp56 reactive T cells
Description
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.
Time Frame
At days 28 (before vaccination), 42 (before vaccination), 56, 70, 84, 100, 180, 365
Secondary Outcome Measure Information:
Title
Incidence of late CMV reactivation after allogeneic hematopoietic stem cell transplant
Description
Will be summarized by dose level using the appropriate descriptive statistics; with estimates of rates obtained by 95% Jeffrey's prior confidence intervals.
Time Frame
From day 85 to 365
Title
Incidence of non-relapse mortality after allogeneic hematopoietic stem cell transplant
Description
Will be summarized by dose level using the appropriate descriptive statistics; with estimates of rates obtained by 95% Jeffrey's prior confidence intervals.
Time Frame
Up to 2 years
Other Pre-specified Outcome Measures:
Title
Number of T cells
Description
Includes CD4 T-cells, CD8 T-cells, delta gamma T-cells, and natural killer T-cells. Will be modeled as a function of time (treated as discrete) and random subject effect (through use of an auto-regressive covariance structure) with a linear mixed model. Mean differences of interest (i.e., changes after vaccination) will be evaluated by using Holm-Bonferroni adjusted tests on the appropriate contrasts of model estimates. All model assumptions will be evaluated graphically, and transformations will be applied as appropriate.
Time Frame
1 year
Title
T cell receptor diversity
Description
Measured by Vbeta spectra-typing. Will be modeled as a function of time (treated as discrete) and random subject effect (through use of an auto-regressive covariance structure) with a linear mixed model. Mean differences of interest (i.e., changes after vaccination) will be evaluated by using Holm-Bonferroni adjusted tests on the appropriate contrasts of model estimates. All model assumptions will be evaluated graphically, and transformations will be applied as appropriate.
Time Frame
1 year
Title
Incidence of adverse events
Description
Toxicities and adverse events (as per Common Terminology Criteria for Adverse Events version 5.0) will be summarized by attribution and grade using frequencies and relative frequencies.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
George L Chen
Organizational Affiliation
Roswell Park Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States

12. IPD Sharing Statement

Learn more about this trial

A Cytomegalovirus-Directed Vaccine (CMV-alphaDC1) for Preventing Cytomegalovirus Infection or Reactivation in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

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