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

NCT05589844 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: I 1289721NCI-2022-05780
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Cytomegaloviral Infection; Hematopoietic and Lymphoid System Neoplasm

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  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

  From day 85 to 365

• Incidence of non-relapse mortality after allogeneic hematopoietic stem cell transplant

  Up to 2 years

Other Outcomes (3)

• Number of T cells

  1 year

• T cell receptor diversity

  1 year

• Incidence of adverse events

  Up to 2 years

Study Arms (1)

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.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Biospecimen Collection; Biological: CMV pp65 Peptide-loaded Alpha-type-1 Polarized Dendritic Cell Vaccine

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo standard of care allogeneic hematopoietic stem cell transplant

Also known as: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Treatment (CMV-alphaDC1)

Biospecimen Collection PROCEDURE

Correlative studies

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (CMV-alphaDC1)

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

Given intradermally

Also known as: CMV pp65 Peptide-loaded Alpha-type-1 Polarized DC Vaccine, Cytomegalovirus pp65 Peptide Loaded Alpha-type 1 Polarized Dendritic Cell Vaccine

Treatment (CMV-alphaDC1)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Cytomegalovirus Infections

Interventions

Stem Cell Transplantation; Specimen Handling

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• George L Chen

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2022
• First Posted: October 21, 2022
• Study Start: March 1, 2023
• Primary Completion: November 16, 2024
• Study Completion: November 16, 2025
• Last Updated: April 27, 2023

Record last verified: 2023-04

Locations

US (1)