Clinical trial NCT05589844: 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
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Cytomegaloviral Infection
Hematopoietic and Lymphoid System Neoplasm
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
First posted: 2022-10-21
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Incidence of dose limiting toxicities
timeFrame: Up to 2 years
measure: Number of multifunctional CMV antigen specific T cells
timeFrame: At days 28 (before vaccination), 42 (before vaccination), 56, 70, 84, 100, 180, 365
measure: Number of CMV pp56 reactive T cells
timeFrame: At days 28 (before vaccination), 42 (before vaccination), 56, 70, 84, 100, 180, 365
Secondary outcomes:
measure: Incidence of late CMV reactivation after allogeneic hematopoietic stem cell transplant
timeFrame: From day 85 to 365
measure: Incidence of non-relapse mortality after allogeneic hematopoietic stem cell transplant
timeFrame: Up to 2 years
Other outcomes:
measure: Number of T cells
timeFrame: 1 year
measure: T cell receptor diversity
timeFrame: 1 year
measure: Incidence of adverse events
timeFrame: Up to 2 years
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: George L Chen
role: PRINCIPAL_INVESTIGATOR
References: