Multi-antigen CMV-Modified Vaccinia Ankara Vaccine in Treating Pediatric Patients With Positive Cytomegalovirus Undergoing Donor Stem Cell Transplant

NCT03354728 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 17236NCI-2017-02046
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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. Multi-antigen CMV-modified vaccinia ankara vaccine may help people resist CMV life-threatening complications.

Conditions

Cytomegaloviral Infection; Hematopoietic Cell Transplant Recipient

Outcome Measures

Primary Outcomes (6)

• Optimal dose (Phase I)

  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.

  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.

  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.

  At 100 days post-HCT

• Severe (grade 3-4) acute graft versus host disease (aGVHD)

  Within 2 weeks from each vaccination

• Incidence of grade 3-4 adverse events

  Will be graded per CTCAE version 4.0.

  Within 2 weeks from each vaccination

Secondary Outcomes (16)

• Time-to viremia

  Number of days from transplant to the date of > 1250 IU/mL, assessed up to 1 year

• Duration of viremia

  Up to 1 year

• Incidence of late CMV viremia

  > 100 and =< 365 days post-HCT

• Use of antiviral drugs (triggered by rising CMV viremia or viremia >= 3,750 IU/ml)

  Up to 1 year, rising CMV viremia or viremia >= 3,705

• Cumulative number of CMV specific antiviral treatment days

  Up to 1 year

Study Arms (1)

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.

Other: Laboratory Biomarker Analysis; Biological: Multi-peptide CMV-Modified Vaccinia Ankara Vaccine

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Supportive Care (multi-antigen CMV-modified vaccinia ankara)

Multi-peptide CMV-Modified Vaccinia Ankara Vaccine BIOLOGICAL

Given IM

Also known as: CMV-MVA Triplex Vaccine, Multi-antigen CMV-Modified Vaccinia Ankara Vaccine

Supportive Care (multi-antigen CMV-modified vaccinia ankara)

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Cytomegalovirus Infections

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Officials

• Anna Pawlowska

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2017
• First Posted: November 28, 2017
• Study Start: May 11, 2018
• Primary Completion (Estimated): December 11, 2026
• Study Completion (Estimated): December 11, 2026
• Last Updated: October 6, 2025

Record last verified: 2025-10

Locations

US (1)