This randomized phase II trial studies how well multi-antigen cytomegalovirus (CMV)-modified vaccinia Ankara vaccine works in reducing CMV related complications in patients with blood cancer who are undergoing donor stem cell transplant. Vaccines made from a gene-modified virus may help the body build an effective immune response to kill cancer cells.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE
City of Hope Medical Center
Duarte, California, United States
Northside Hospital
Atlanta, Georgia, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Cytomegalovirus (CMV) events
Will include any CMV reactivation (detection of \>= 1250 U/mL plasma), low-level reactivation prompting antiviral therapy, or CMV disease (defined by histology) prior to day 100 post-hematopoietic cell transplantation (HCT).
Time frame: Up to 3 years
Non-relapse mortality (NRM)
Time frame: At 100 days post HCT
Severe (grade 3-4) acute graft versus host disease (GVHD)
Time frame: Up to 3 years
Grade 3-4 adverse events probably/definitely related to the vaccination and modified vaccinia Ankara vector persistence
Time frame: Up to 3 years
Duration of viremia
The primary statistical analyses will compare vaccine and placebo regarding hazards of CMV events from injection to day 100. Events prior to injection will inform Kaplan Meier estimates for both arms to obtain unbiased estimates of reactivation rates applicable to all transplanted subjects on each arm.
Time frame: Up to 3 years
Duration of anti-CMV therapy
Time frame: Up to 3 years
Peak CMV polymerase chain reaction value
Time frame: Up to 3 years
Recurrence of CMV viremia
Time frame: Up to 3 years
Incidence of late CMV reactivation or disease
Time frame: Up to 3 years
Time to engraftment
Time frame: Up to 3 years
Incidence of acute GVHD
Will be scored using Keystone consensus criteria. Whenever possible, acute GVHD will be confirmed histologically with microscopic review.
Time frame: Up to 3 years
Incidence of chronic GVHD
Time frame: Up to 3 years
Relapse
Time frame: Up to 3 years
Non-relapse mortality
Time frame: Up to 3 years
All-cause mortality
Time frame: Up to 3 years
Infections
Time frame: Up to 3 years
Overall survival
Time frame: Up to 3 years
Levels of CMV-specific T cell immunity
Will also assess immunophenotyping and function.
Time frame: Up to 3 years
Natural killer cell function
Will assess cytotoxicity of NK cells against K562 target cell line compared with control (% killing) and cytokine production using flow-cytometry with intra-cellular staining of gamma-interferon and other cytokines (% of NK cells producing these cytokines).
Time frame: Up to 3 years
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