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

NCT ID: NCT05589844

Last Updated: 2023-04-27

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-31
• Study Completion Date: 2025-11-16

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.

Conditions

Cytomegaloviral Infection; Hematopoietic and Lymphoid System Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Treatment (CMV-alphaDC1)

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.

Group Type: EXPERIMENTAL

Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Type: PROCEDURE

Undergo standard of care allogeneic hematopoietic stem cell transplant

Biospecimen Collection

Intervention Type: PROCEDURE

Correlative studies

CMV pp65 Peptide-loaded Alpha-type-1 Polarized Dendritic Cell Vaccine

Intervention Type: BIOLOGICAL

Given intradermally

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation

Undergo standard of care allogeneic hematopoietic stem cell transplant

Intervention Type: PROCEDURE

Biospecimen Collection

Correlative studies

Intervention Type: PROCEDURE

CMV pp65 Peptide-loaded Alpha-type-1 Polarized Dendritic Cell Vaccine

Given intradermally

Intervention Type: BIOLOGICAL

Other Intervention Names

Allogeneic; Allogeneic Hematopoietic Cell Transplantation; Allogeneic Stem Cell Transplantation; HSC; HSCT; Stem Cell Transplantation, Allogeneic; Biological Sample Collection; Biospecimen Collected; Specimen Collection; CMV pp65 Peptide-loaded Alpha-type-1 Polarized DC Vaccine; Cytomegalovirus pp65 Peptide Loaded Alpha-type 1 Polarized Dendritic Cell Vaccine

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Roswell Park Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

George L Chen

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Locations

Roswell Park Cancer Institute

Buffalo, New York, United States

Countries

United States

Other Identifiers

NCI-2022-05780

Identifier Type: REGISTRY

Identifier Source: secondary_id

I 1289721

Identifier Type: OTHER

Identifier Source: secondary_id

I 1289721

Identifier Type: -

Identifier Source: org_study_id