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

Active:	Yes
Cancer Type:	Cancer-Related Syndrome Hodgkin Lymphoma Leukemia Lymphoma Myelodysplastic Syndromes (MDS) Non-Hodgkin Lymphoma	NCT ID:	NCT07020533
Trial Phases:	Phase I	Protocol IDs:	24168 (primary) NCI-2025-03633
Eligibility:	18 - 75 Years, Male and Female	Study Type:	Prevention
Study Sponsor:	City of Hope Comprehensive Cancer Center
NCI Full Details:	http://clinicaltrials.gov/show/NCT07020533

Summary

This phase Ib trial tests the safety, side effects, and how well cytomegalovirus (CMV)-modified vaccinia Ankara (MVA) Triplex vaccine works in enhancing CMV-specific immunity and preventing CMV viremia in patients undergoing haploidentical hematopoietic stem cell transplant. Haploidentical stem cell transplantation (haploHCT) has advanced to become the predominant procedure for patients lacking a matched donor. Compared to matched related donor transplants, the rate of significant CMV infection is higher in patients undergoing a haploHCT. Significant CMV infection is associated with an increased risk of complications and death. Vaccination is the main preventative approach to limit complications and death in immunocompromised patients at high risk of post-stem cell transplant infections. CMV-MVA Triplex vaccine, is a CMV vaccine based on the attenuated poxvirus, modified vaccinia Ankara (MVA), developed to enhance CMV-specific immunity in both healthy stem cell transplant donors and stem cell transplant patients to prevent significant CMV infection post-stem cell transplant. Giving CMV-MVA triplex vaccine may be safe, tolerable and/or effective in enhancing cytomegalovirus (CMV)-specific immunity and preventing CMV viremia in patients undergoing a haploHCT.

Objectives

PRIMARY OBJECTIVE:
I. To evaluate whether the multi-peptide cytomegalovirus-modified vaccinia Ankara vaccine (CMV-MVA Triplex [Triplex]) vaccination of stem cell donors (D) and recipients (R) alone or in combination with letermovir safely protects against CMV events for day (d)100 in the absence of preemptive therapy (PET) and to determine the recommended duration of letermovir use as phase 2 modality in the haploidentical stem cell transplantation (haploHCT)-R.

SECONDARY OBJECTIVES:
I. To evaluate safety of Triplex in the haploHCT-R.
II. To evaluate cumulative incidence of CMV events up to d180 post-hematopoietic stem cell transplant (HCT).
III. To evaluate CMV viremia levels over time in the HCT-R.
IV. To evaluate cumulative incidence of CMV disease.
V. To evaluate use of PET by the HCT-R.

EXPLORATORY OBJECTIVES:
I. To assess levels and durability of CMV specific T cell immunity.
II. To assess polyfunctional T cell responses and cell-surface memory markers until d180 post-HCT.

OUTLINE:

DONORS: Participants receive CMV-MVA Triplex vaccine intramuscularly (IM) once and then receive granulocyte colony stimulating factor (G-CSF) on study. Additionally, participants undergo apheresis on study as well as blood sample collection on study and may optionally undergo blood sample collection during follow up.

RECIPIENTS: Patients are assigned to 1 of 3 modalities.

MODALITY 1: Patients receive myeloablative conditioning during screening and undergo HCT from haploidentical vaccinated donor on day 0. Patients receive CMV-MVA Triplex vaccine IM once daily (QD) on days 28, 56 and 100 and receive letermovir intravenously (IV) over 1 hour or orally (PO) QD on days 7 to 100. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection throughout the study.

MODALITY 2: Patients receive myeloablative conditioning during screening and undergo HCT from haploidentical vaccinated donor on day 0. Patients receive CMV-MVA Triplex vaccine IM QD on days 28, 56 and 100 and receive letermovir IV over 1 hour or PO QD on days 7 to 28. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection throughout the study.

MODALITY 3: Patients receive myeloablative conditioning during screening and undergo HCT from haploidentical vaccinated donor on day 0. Patients receive CMV-MVA Triplex vaccine IM QD on days 28, 56 and 100. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection throughout the study.

After completion of study treatment, patients are followed up every 2 weeks until day 180 and then at day 365.

Treatment Sites in Georgia

Northside Hospital Cancer Institute - Bone Marrow Transplant (BMT)
1000 Johnson Ferry Road NE
Atlanta, GA 30342
404-851-8523

Doctors:

Scott R. Solomon MD

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.