Multi-antigen CMV-Modified Vaccinia Ankara Vaccine in Reducing CMV Related Complications in Patients With Blood Cancer Undergoing Donor Stem Cell Transplant

PRIMARY OBJECTIVES: I. To determine if multi-antigen CMV-modified vaccinia Ankara vaccine (CMV-modified vaccinia Ankara \[MVA\] triplex) reduces the frequency of CMV events, defined as reactivation or CMV disease in CMV+, haploidentical hematopoietic cell transplantation (haploHCT) recipients. SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of CMV-MVA triplex in vaccinated, haploHCT recipients by assessing the following: non-relapse mortality (NRM) at 100 days post hematopoietic cell transplantation (HCT), severe (grade 3-4) acute graft versus host disease (GVHD), and grade 3-4 adverse events (AEs) probably or definitely related to the vaccination within 2 weeks from each vaccination. II. To characterize CMV related events in recipients of CMV-MVA triplex compared to placebo, by assessing time to viremia (number of days from transplantation to the date of \>= 1250 IU/mL), duration of viremia, recurrence of viremia, incidence of late CMV viremia/disease (\> 100 and =\< 360 days post HCT), use of antiviral drugs (triggered by clinically significant viremia of \>= 1250 IU/mL), cumulative number of CMV specific antiviral treatment days. III. To evaluate the impact of CMV-MVA triplex on transplant related outcomes by assessing the incidence of acute graft versus host disease (aGVHD), chronic GVHD, relapse, non-relapse mortality, all-cause mortality, infections. IV. To determine if CMV-MVA triplex increases levels, function and kinetics of CMV-specific T cell immunity in vaccinated compared to placebo treated, CMV seropositive HCT-recipients. V. To determine whether vaccination induces adaptive natural killer (NK) cell population changes, and increase in the highly cytotoxic memory NKG2C+ NK cell. VI. To compare GVHD biomarkers between the vaccine and placebo groups. OUTLINE: Patients are randomized into 1 of 2 arms. ARM I: Patients receive multi-antigen CMV-modified vaccinia Ankara vaccine intramuscularly (IM) on days 28 and 56 post-HCT. ARM II: Patients receive placebo IM on days 28 and 56 post-HCT. After completion of study treatment, patients are followed up at 100, 140, 180, 270, and 365 days, and then periodically for 3 years.