Actively Recruiting

Phase 1
Age: 18Years - 75Years
All Genders
Healthy Volunteers
ID07020533

A Phase 1b Trial of CMV-MVA Triplex Vaccine in Haploidentical Stem Cell Donors and Recipients to Enhance CMV-Specific Immunity and Prevent CMV Viremia in Recipients of Hematopoietic Stem Cell Transplant

Led by City of Hope Medical Center · Updated on 2026-03-27

46

Participants Needed

3

Research Sites

N/A

Total Duration

On this page

Sponsors

C

City of Hope Medical Center

Lead Sponsor

N

National Cancer Institute (NCI)

Collaborating Sponsor

AI-Summary

What this Trial Is About

Researchers are evaluating the CMV-modified vaccinia Ankara (MVA) Triplex vaccine in patients receiving haploidentical hematopoietic stem cell transplants (haploHCT) to enhance immunity against cytomegalovirus (CMV) and prevent CMV viremia. This phase Ib trial focuses on the safety, side effects, and immune response benefits of the vaccine in both donors and recipients. HaploHCT is a common transplant method for patients without matched donors, but it carries a higher risk of CMV infections that can lead to serious complications and death. Vaccination may help reduce these risks by boosting CMV-specific immunity in this vulnerable group. In this study, stem cell donors receive a single intramuscular dose of the CMV-MVA Triplex vaccine followed by granulocyte colony-stimulating factor (G-CSF) and apheresis. Recipients undergo myeloablative conditioning before transplant and are assigned to one of three treatment groups. Each group receives the CMV-MVA Triplex vaccine intramuscularly on days 28, 56, and 100 after transplant. Some groups also receive letermovir, an antiviral drug, either intravenously or orally for varying durations (days 7 to 28 or days 7 to 100). Treatment continues unless disease progression or unacceptable toxicity occurs. Participants undergo blood sample collections throughout the study to monitor immune responses and CMV levels. After treatment, recipients are followed every two weeks until day 180, then again at day 365 to assess outcomes. Researchers will measure CMV reactivation requiring antiviral therapy and CMV disease up to day 100 post-transplant as primary outcomes. Secondary and exploratory outcomes include vaccine safety, incidence of graft-versus-host disease, survival, and detailed immune cell responses. The total participation may last up to one year post-transplant.

CONDITIONS

Brief Title

A Vaccine (CMV-MVA Triplex Vaccine) for the Enhancement of CMV-Specific Immunity and the Prevention of CMV Viremia in Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplant

Who Can Participate

Age: 18Years - 75Years
All Genders
Healthy Volunteers

Eligibility Criteria

Eligible

You may qualify if you...

  • Donors: Provide documented informed consent.
  • Donors: Age between 18 and 75 years.
  • Donors: Women of childbearing potential must have a negative pregnancy test.
  • Donors: Agree to use effective birth control or abstain from heterosexual activity before and up to 90 days after vaccination.
  • Recipients: Provide documented informed consent.
  • Recipients: Willing to comply with study and follow-up procedures for one year post-transplant.
  • Recipients: Age between 18 and 75 years.
  • Recipients: Planned haploidentical peripheral blood stem cell or bone marrow transplant for specified hematologic malignancies.
  • Recipients: Receiving myeloablative or reduced intensity conditioning.
  • Recipients: CMV seropositive.
  • Recipients: Eligible haploidentical donors with required HLA mismatches.
  • Recipients: Planned transplant with minimal to no T-cell depletion of graft.
  • Recipients: Meet specific organ function and infectious disease testing criteria.
  • Recipients: Women of childbearing potential must have negative pregnancy test.
  • Recipients: Agree to use effective birth control or abstain from heterosexual activity before and up to 90 days post-transplant.
Not Eligible

You will not qualify if you...

  • Donors: Prior transplant before vaccination day.
  • Donors: Received chemotherapy, radiation, biological, or immunotherapy within 21 days before vaccination.
  • Donors: Received any vaccine within 30 days before or after study vaccine.
  • Donors: Unfit for stem cell mobilization or apheresis, including abnormal blood counts or stroke history.
  • Donors: Sickling hemoglobinopathies.
  • Donors: Impaired cardiac function excluding minor ECG changes.
  • Donors: Severe psychiatric illness or mental deficiency preventing compliance or consent.
  • Donors: Pregnant or breastfeeding women.
  • Donors: Other conditions judged unsafe for study participation.
  • Donors: Unable to comply with study procedures.
  • Recipients: Previous investigational CMV vaccine or experimental anti-CMV chemotherapy in last 6 months.
  • Recipients: Planned live attenuated or certain subunit/killed vaccines from transplant to day 70.
  • Recipients: Use of T-cell depleting agents or certain antiviral medications affecting CMV during study window.
  • Recipients: Prophylactic CMV immunoglobulin or antiviral treatments except letermovir before day 100.
  • Recipients: Disease-based radiation therapy (non-total body) during study window.
  • Recipients: Concurrent enrollment in other investigational drug trials affecting CMV.
  • Recipients: Active autoimmune conditions requiring systemic immunosuppression in past 5 years.
  • Recipients: Poor risk disease status or complicated prior therapy.
  • Recipients: Pregnant or breastfeeding women.
  • Recipients: Other conditions judged unsafe for study participation.
  • Recipients: Unable to comply with study procedures.

AI-Screening

AI-Powered Screening

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

Screening and enrollment visit

Donor Vaccination and Procedures

Duration - Up to 1 week before transplant

Donors receive a single CMV-MVA Triplex vaccine intramuscularly, followed by granulocyte colony stimulating factor (G-CSF) administration. Donors undergo apheresis and blood sample collection during this period, with optional blood sample collection during follow-up.

1 to 2 visits including vaccination and apheresis

Recipient Conditioning and Transplant

Duration - Approximately 1 week

Recipients undergo myeloablative conditioning and receive hematopoietic stem cell transplant from a haploidentical vaccinated donor on day 0.

1 visit on transplant day

Recipient Treatment

Duration - Up to 100 days post-transplant

Recipients receive CMV-MVA Triplex vaccine intramuscularly on days 28, 56, and 100. Depending on modality, recipients receive letermovir daily either from days 7 to 100, days 7 to 28, or not at all. Treatment continues in the absence of disease progression or unacceptable toxicity. Blood samples are collected throughout this period.

3 vaccine visits and daily letermovir administration as applicable

Follow-up

Duration - Up to 1 year post-transplant

After treatment completion, recipients are followed every 2 weeks until day 180 and again at day 365 for ongoing monitoring and assessments.

Biweekly visits until day 180 and 1 visit at day 365

Trial Site Locations

Total: 3 locations

1

City of Hope Medical Center

Duarte, California, United States, 91010

Actively Recruiting

2

Northside Hospital

Atlanta, Georgia, United States, 30342

Actively Recruiting

3

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

Actively Recruiting

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How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

SEQUENTIAL

Primary Purpose

PREVENTION

Number of Arms

4

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