Cytomegaloviral InfectionPhase 1/2NCT03354728
Multi-antigen CMV-Modified Vaccinia Ankara Vaccine in Treating Pediatric Patients With Positive Cytomegalovirus Undergoing Donor Stem Cell Transplant
A Phase 1/2 study testing Laboratory Biomarker Analysis and Multi-peptide CMV-Modified Vaccinia Ankara Vaccine in people with Cytomegaloviral Infection and Hematopoietic Cell Transplant Recipient, run by City of Hope Medical Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Cytomegaloviral Infection, Hematopoietic Cell Transplant Recipient
- What is being tested?
- Laboratory Biomarker Analysis and Multi-peptide CMV-Modified Vaccinia Ankara Vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Aug 2018to 11 Dec 2026
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- All subjects (or their guardians) must have the ability to understand and the willingness to sign a written informed consent; age appropriate assent will be obtained per institutional guidelines; to allow non-English patients to participate in this study, bilingual health services will be provided in the appropriate language when feasible
- Participant must be willing to comply with study and/or follow-up procedures, including willingness to be followed for one year post-HCT
- Planned allogenic (allo)-HCT, with 9/10 or 10/10 (A, B, C, DRB1, DQB1) high/intermediate resolution HLA donor allele matching and with no T-cell depletion of graft
- Planned related HCT with molecular 3/6 HLA donor allele matching (haploidentical) (for phase I only)
- CMV seropositive at the time of HCT
- Conditioning and immunosuppressive regimens according to institutional guidelines are permitted
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- Negative serum or urine beta-human chorionic gonadotropin (HCG) test (female patient of childbearing potential only) within two weeks of registration
- Seronegative for human immunodeficiency virus (HIV), hepatitis C virus (HCV); if hepatitis B virus (HBV) core seropositive, absence of HBV deoxyribonucleic acid (DNA) within 2 months of registration
- Agreement by females of childbearing potential and sexually active males to use an effective method of contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for up to 90 days post-HCT; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
Who cannot join
- TRANSPLANT RELATED CRITERIA: Patients undergoing cord blood transplant (CB-HCT)
- Any prior investigational CMV vaccine
- Anti-CMV therapy in the last 6 months
- Live attenuated vaccines
- Medically indicated subunit (Engerix-B for HBV; Gardasil for human papillomavirus [HPV]) or killed vaccine (e.g. influenza, pneumococcal)
- Allergy treatment with antigens injections
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- Alemtuzumab, cyclophosphamide, ATG or any equivalent in vivo T-cell depleting agent; Note: Pre-transplant ATG is permitted
- Antiviral medications with known therapeutic effects on CMV such as ganciclovir (GCV)/valine (VAL), FOS, Cidofovir, CMX-001, maribavir; acyclovir has no known therapeutic efficacy against CMV and is allowable as standard of care to prevent herpes simplex virus (HSV)
- Prophylactic therapy with CMV immunoglobulin or prophylactic antiviral CMV treatment; intravenous immunoglobulin therapy (IVIG) is allowed
- Other investigational product-concurrent enrollment in other clinical trials using any investigational new drug (IND) drugs with unknown effects on CMV or with unknown toxicity profiles is prohibited
- Other medications that might interfere with the evaluation of the investigational product
- Patients with congenital immune deficiency
- Patients with active autoimmune conditions requiring systemic immunosuppressive therapy within the previous 5 years are not eligible, the exception to this is patients with aplastic anemia, who are eligible
- Pregnant women and women who are lactating; CMV-MVA Triplex risks to pregnant women are unknown; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the administered vaccine, also breastfeeding should be discontinued if the mother is enrolled on this study
- Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., social/psychological issues, etc
- Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issue related to feasibility/logistics)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
City of Hope Medical Center
Duarte, California, 91010
Anna B. Pawlowska, 626-301-8442, apawlows@coh.org
Anna B. Pawlowska
About this study
Official title: A Phase 1/2 Clinical Study to Evaluate the Optimal Dose and the Protective Effect of CMV-MVA Triplex Vaccine in Pediatric Patients Receiving an Allogeneic Hematopoietic Stem Cell Transplant
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Being tested
- Laboratory Biomarker Analysis, Multi-peptide CMV-Modified Vaccinia Ankara Vaccine
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
Multi-peptide CMV-Modified Vaccinia Ankara VaccineBiological
Also called CMV-MVA Triplex Vaccine, Multi-antigen CMV-Modified Vaccinia Ankara Vaccine
Given IM
| Study group | Role | What they receive |
|---|---|---|
| Supportive Care (multi-antigen CMV-modified vaccinia ankara) | Experimental | Patients receive multi-antigen CMV-modified vaccinia ankara vaccine IM on days 28 and 56 post-HCT. Receives: Other: Laboratory Biomarker Analysis; Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Optimal dose (Phase I)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: At 100 days post-HCT
Severe (grade 3-4) acute graft versus host disease (aGVHD)
Measured: Within 2 weeks from each vaccination
Incidence of grade 3-4 adverse events
Will be graded per CTCAE version 4.0.
Measured: Within 2 weeks from each vaccination
Secondary outcomes (16)
Time-to viremia
Measured: Number of days from transplant to the date of > 1250 IU/mL, assessed up to 1 year
Duration of viremia
Measured: Up to 1 year
Incidence of late CMV viremia
Measured: > 100 and =< 365 days post-HCT
Use of antiviral drugs (triggered by rising CMV viremia or viremia >= 3,750 IU/ml)
Measured: Up to 1 year, rising CMV viremia or viremia >= 3,705
Cumulative number of CMV specific antiviral treatment days
Measured: Up to 1 year
Time to engraftment
Measured: Up to 1 year
Incidence of acute graft versus host disease (aGVHD)
Measured: Up to 1 year
Chronic GVHD (cGVHD)
Measured: Up to 1 year
Relapse defined by bone marrow and/or imaging studies
Measured: Up to 1 year
Non-relapse mortality
Measured: Up to 1 year
All-cause mortality
Measured: Up to 1 year
Infections
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 1 year post-HCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2017
- Study start31 Aug 2018
- Primary completion11 Dec 2026 (estimated)
- Study completion11 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cytomegaloviral InfectionStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Anna Pawlowska, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03354728
- Sponsor's protocol ID
- 17236
- Other IDs
- NCI-2017-02046, 17236
- Status last verified
- Oct 2026
- First submitted
- 6 Nov 2017
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No