This phase I/II trial studies the side effects and best dose of multi-antigen cytomegalovirus (CMV)-modified vaccinia ankara vaccine and to see how well it works in treating pediatric patients with positive cytomegalovirus who are undergoing donor stem cell transplant. Multi-antigen CMV-modified vaccinia ankara vaccine may help people resist CMV life-threatening complications.
PRIMARY OBJECTIVES: I. To investigate the optimal dose of multi-antigen CMV-modified vaccinia ankara vaccine (Triplex) in CMV-positive pediatric patients receiving human leukocyte antigen (HLA) matched, mismatched, or haploid-identical hematopoietic cell transplantation (HCT). (Phase I) II. To evaluate the safety profile of Triplex in this patient population. (Phase I) III. To determine if Triplex reduces the frequency of CMV events when compared to historical data. (Phase II) SECONDARY OBJECTIVES: I. To characterize CMV reactivation and disease by assessing: time to CMV reactivation, duration of viremia, recurrence of viremia, incidence of late CMV viremia/disease (defined as \> 100 days and =\< 365 days post HCT), use of anti-viral drugs triggered by rising CMV viremia or viremia \>= 3750 IU/mL, cumulative number of CMV specific antiviral treatment days. II. To evaluate the impact of Triplex on transplant related outcomes by assessing the incidence of acute and chronic graft versus host disease (GVHD), relapse, non-relapse mortality (NRM), all-cause mortality, infections. III. To investigate the impact of Triplex on cellular immunity by investigating: the level, function and kinetics of CMV-specific T-cell immunity, the changes in adaptive natural killer (NK) cell population and highly cytotoxic memory NKG2C+ NK cells, and changes in GVHD biomarkers. OUTLINE: This is a phase I, dose-escalation study followed by a phase II study. Patients receive multi-antigen CMV-modified vaccinia ankara vaccine intramuscularly (IM) on days 28 and 56 post-HCT. After completion of study treatment, patients are followed up for up to 270 or 365 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
80
Correlative studies
Given IM
City of Hope Medical Center
Duarte, California, United States
RECRUITINGOptimal dose (Phase I)
Time frame: Up to 1 year
Incidence of adverse events (Phase I)
Adverse events will be characterized using the descriptions and grading scales according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time frame: Up to 1 year
Cytomegalovirus (CMV) events (reactivation >= 1250 IU/mL), or viremia treated by anti-viral therapy, or detection of CMV by histology (Phase II)
Will be assessed with exact 90% confidence bounds.
Time frame: Prior to day 100 post-hematopoietic cell transplantation (HCT) or viremia treated by anti-viral therapy, or detection of CMV by histology
Non-relapse mortality
Will be compared to historical controls at the final analysis, and a 90% lower confidence bound on the difference in 12-month event free survival will be produced.
Time frame: At 100 days post-HCT
Severe (grade 3-4) acute graft versus host disease (aGVHD)
Time frame: Within 2 weeks from each vaccination
Incidence of grade 3-4 adverse events
Will be graded per CTCAE version 4.0.
Time frame: Within 2 weeks from each vaccination
Time-to viremia
Time frame: Number of days from transplant to the date of > 1250 IU/mL, assessed up to 1 year
Duration of viremia
Time frame: Up to 1 year
Incidence of late CMV viremia
Time frame: > 100 and =< 365 days post-HCT
Use of antiviral drugs (triggered by rising CMV viremia or viremia >= 3,750 IU/ml)
Time frame: Up to 1 year, rising CMV viremia or viremia >= 3,705
Cumulative number of CMV specific antiviral treatment days
Time frame: Up to 1 year
Time to engraftment
Time frame: Up to 1 year
Incidence of acute graft versus host disease (aGVHD)
Time frame: Up to 1 year
Chronic GVHD (cGVHD)
Time frame: Up to 1 year
Relapse defined by bone marrow and/or imaging studies
Time frame: Up to 1 year
Non-relapse mortality
Time frame: Up to 1 year
All-cause mortality
Time frame: Up to 1 year
Infections
Time frame: Up to 1 year
Levels of CMV-specific T cell immunity
Will be combined with immunophenotyping and functional studies. The data analysis for estimating the effect of vaccination on cellular immunity will necessarily be more exploratory in nature. The longitudinal CMV-specific cellular assay data will be modeled on a logarithmic scale, using a generalized estimating equation approach to accommodate the stochastic dependence through time. This produces an estimated multiplicative effect of vaccination, qualified by a valid estimate of variability.
Time frame: Up to 1 year post-HCT
Kinetics of CMV-specific T cell immunity
The data analysis for estimating the effect of vaccination on cellular immunity will necessarily be more exploratory in nature. The longitudinal CMV-specific cellular assay data will be modeled on a logarithmic scale, using a generalized estimating equation approach to accommodate the stochastic dependence through time. This produces an estimated multiplicative effect of vaccination, qualified by a valid estimate of variability.
Time frame: Up to 1 year post-HCT
Natural killer (NK) phenotype
The data analysis for estimating the effect of vaccination on cellular immunity will necessarily be more exploratory in nature. The longitudinal CMV-specific cellular assay data will be modeled on a logarithmic scale.
Time frame: Up to 1 year post-HCT
NK function (cytotoxicity and cytokine production)
The data analysis for estimating the effect of vaccination on cellular immunity will necessarily be more exploratory in nature. The longitudinal CMV-specific cellular assay data will be modeled on a logarithmic scale, using a generalized estimating equation approach to accommodate the stochastic dependence through time. This produces an estimated multiplicative effect of vaccination, qualified by a valid estimate of variability.
Time frame: Up to 1 year post-HCT
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.