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

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.