NCT07020533

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

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 46 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Accepted

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.

Detailed description

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.

Conditions

• Accelerated Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive
• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Chronic Lymphocytic Leukemia
• Chronic Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive
• Hematopoietic and Lymphatic System Neoplasm
• Hodgkin Lymphoma
• Lymphoblastic Lymphoma
• Myelodysplastic Syndrome
• Myelofibrosis
• Myeloproliferative Neoplasm
• Non-Hodgkin Lymphoma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
OTHER	Electronic Health Record Review	Ancillary studies
PROCEDURE	Haploidentical Hematopoietic Cell Transplantation	Undergo HCT
DRUG	Letermovir	Given IV or PO
BIOLOGICAL	Multi-peptide CMV-Modified Vaccinia Ankara Vaccine	Given IM
PROCEDURE	Myeloablative Conditioning	Receive myeloablative conditioning
PROCEDURE	Pheresis	Undergo apheresis
BIOLOGICAL	Recombinant Granulocyte Colony-Stimulating Factor	Given G-CSF

Timeline

• Start date: 2026-05-08
• Primary completion: 2030-02-14
• Completion: 2030-02-14
• First posted: 2025-06-13
• Last updated: 2026-03-27

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study