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High Dose Flu Vaccine in Treating Children Who Have Undergone Donor Stem Cell Transplant

Phase 2
Completed
Conditions
Hematopoietic Cell Transplantation Recipient
Malignant Neoplasm
Influenza
Interventions
Registration Number
NCT02860039
Lead Sponsor
Vanderbilt-Ingram Cancer Center
Brief Summary

This phase II randomized trial studies how well high dose flu vaccine works in treating children who have undergone done stem cell transplant. Higher dose flu vaccine may build a better immune response and may provide better protection against the flu than the standard vaccine.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine whether high-dose trivalent inactivated influenza vaccine (HD-TIV) compared with standard dose quadrivalent inactivated influenza vaccine (QIV) will increase the probability of achieving a \>= 4-fold rise in hemagglutination-inhibition (HAI) titers, \>= 1:40 HAI titer, or higher geometric mean titer (GMT) to influenza A antigens in pediatric hematopoietic stem cell transplant (HSCT) recipients.

SECONDARY OBJECTIVES:

I. To determine whether HD-TIV compared with standard dose QIV will increase the probability of achieving a \>= 4-fold rise in HAI titers, \>= 1:40 HAI titer, or higher GMT titers to influenza B antigens in pediatric HSCT recipients.

II. To determine the frequency and severity of solicited local injection site adverse events (e.g. pain/ tenderness, redness, and swelling at injection site) with HD-TIV compared to standard QIV in pediatric HSCT recipients.

III. To determine the frequency and severity of solicited systemic adverse events (e.g. fevers, headache, fatigue/malaise, nausea, body ache/myalgia, general activity level, and vomiting) with HD-TIV compared to standard dose QIV in pediatric HSCT recipients.

IV. To define the relationship between HAI titers, in vivo T and B cell phenotype, and in vitro influenza-specific T and B cell response in pediatric HSCT recipients receiving either HD-TIV or standard dose QIV.

V. To correlate HAI responses to microneutralization responses.

VI. To compare the persistent HAI and microneutralization (MN) titers for all four antigen seven months after the last vaccine dose to assess for persistence of antibody titers.

VII. To compare influenza detection by PCR during influenza season in pediatric HSCT recipients receiving either HD-TIV or standard dose QIV.

VIII. To assess HAI and MN response in children vaccinated during year 1 and revaccinated during year 2 using the same antigen dose.

OUTLINE: Patients are randomized to 1 of 2 treatment groups.

GROUP I (Experimental): Patients receive HD-TIV intramuscularly (IM) on day 0 and day 28.

GROUP II (Standard): Patients receive standard dose QIV IM on day 0 and day 28.

After completion of study treatment, patients are followed up at 28-42 days, and at 7 months.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
170
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group 2 - Standard Dose QIVLaboratory Biomarker AnalysisPatients receive standard dose QIV IM on day 0 and day 28.
Group 1 - High Dose TIVTrivalent Influenza VaccinePatients receive HD-TIV intramuscularly (IM) on day 0 and day 28.
Group 2 - Standard Dose QIVQuadrivalent Influenza VaccinePatients receive standard dose QIV IM on day 0 and day 28.
Group 1 - High Dose TIVLaboratory Biomarker AnalysisPatients receive HD-TIV intramuscularly (IM) on day 0 and day 28.
Primary Outcome Measures
NameTimeMethod
Immunogenicity as Measured by the Number of Subjects Who Achieve a 4-fold (or Greater) Rise in Post-vaccination HAI TitersVisit 1 (baseline) was day 0; visit 2 was 28-42 days after visit 1; visit 3 was 28-42 days after visit 2; and visit 4 was 138-222 days after visit 2.

Point estimates and 95% confidence intervals for proportion of subjects achieving seroconversion (4-fold or greater rise in HAI titers from visit 1).

Secondary Outcome Measures
NameTimeMethod
Proportion of Solicited Local and Systemic Adverse EventsUp to 7 days following each vaccination: up to day 7 for vaccine 1 and up to day 35-49 for vaccine 2

The proportion of subjects in each group experiencing at least one solicited AE with 95% posterior credible intervals, separated by vaccine number and adverse event type. AEs were assessed by clinicians using Tables 4 and 5 within section C16 of the protocol.

Solicited injection site AEs included: pain, tenderness, erythema/redness, and swelling/induration. The diameter of any erythema/redness and swelling/induration was measured to evaluate "redness size" and "swelling size." Solicited systemic AEs included: fevers, fatigue/malaise, headache, nausea, body ache/myalgia, generally activity, and vomiting.

T and B Cell Phenotype Assessed by Mass CytometryVisit 1 (baseline) was day 0; visit 2 was 28-42 days after visit 1; visit 3 was 28-42 days after visit 2; and visit 4 was 138-222 days after visit 2.

T and B cell response was assessed at visit 1,visit 2, visit 3, and visit 4.

Results are incomplete due to pending grant funding for laboratory testing. This outcome will be updated once the funding has been obtained and results are available.

T and B Cell Response Assessed by Mass Cytometry and In-vitro Functionality AssaysVisit 1 (baseline) was day 0; optional visit 1 was 5-10 days after visit 1; visit 2 was 28-42 days after visit 1; optional visit 2 was 5-10 days after visit 2; visit 3 was 28-42 days after visit 2; and visit 4 was 138-222 days after visit 2.

T and B cell response was assessed at visit 1, an optional visit 5-10 days after visit 1, visit 2, an optional visit 5-10 days after visit 2, visit 3, and visit 4.

Results are pending due to pending grant funding for laboratory testing. This outcome will be updated once the funding has been obtained and results are available.

Percentage of Individuals in Each Group Who Test Positive for InfluenzaDuring the influenza season, up to 6 months

The percentage of breakthrough flu in vaccinated participants, separated by treatment group.

Trial Locations

Locations (9)

Nationwide Children's Hospital

🇺🇸

Columbus, Ohio, United States

Texas Children's Hospital

🇺🇸

Houston, Texas, United States

UCSF Children's Hospital

🇺🇸

San Francisco, California, United States

St. Jude Children's Research Hospital

🇺🇸

Memphis, Tennessee, United States

Vanderbilt-Ingram Cancer Center

🇺🇸

Nashville, Tennessee, United States

Children's Mercy Hospital

🇺🇸

Kansas City, Missouri, United States

Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

Cincinnati Children's Hospital

🇺🇸

Cincinnati, Ohio, United States

Seattle Children's Hospital Research Institute

🇺🇸

Seattle, Washington, United States

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