High vs. Standard Dose Flu Vaccine in Adult Stem Cell Transplant Recipients

Phase 2

Completed

Conditions: Hematopoietic Cell Transplantation

Interventions: Other: Laboratory Biomarker Analysis
Biological: Quadrivalent Inactivated Influenza Vaccine
Biological: Trivalent Influenza Vaccine

Registration Number: NCT03179761

Lead Sponsor: Vanderbilt-Ingram Cancer Center

Brief Summary: This randomized phase II studies the side effects of high-dose trivalent influenza vaccine or standard-dose quadrivalent inactivated influenza and how well they work in treating adult patients undergoing stem cell transplant. Season influenza can cause more severe infections in patients who have had a stem cell transplant since their immune system doesn't work as well. Influenza vaccine may provide better protection against flu in adults.

Detailed Description: PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

I. To determine whether HD-TIV compared with SD-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 adult 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 SD-QIV in adult 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 SD-QIV in adult 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 adult HSCT recipients receiving either HD-TIV or SD-QIV.

V. To correlate HAI responses to microneutralization responses. VI. To compare the persistent HAI and microneutralization assay (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 polymerase chain reaction (PCR) during influenza season in adult HSCT recipients receiving either HD-TIV or standard dose QIV.

OUTLINE: Patients are randomized into 1 of 2 groups.

GROUP I: Patients receive HD-TIV intramuscularly once at baseline and once between 28-42 days.

GROUP II: Patients receive SD-QIV intramuscularly once at baseline and once between 28-42 days.

After completion of study treatment, patients are contacted at 1-3 and 8-10 days after each vaccination visit.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 124

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group I (HD-TIV)	Trivalent Influenza Vaccine	Patients received HD-TIV intramuscularly once at baseline (day 0) and again between 28-42 days later.
Group I (HD-TIV)	Laboratory Biomarker Analysis	Patients received HD-TIV intramuscularly once at baseline (day 0) and again between 28-42 days later.
Group 2(SD-QIV)	Quadrivalent Inactivated Influenza Vaccine	Patients received SD-QIV intramuscularly once at baseline (day 0) and again between 28-42 days later.
Group 2(SD-QIV)	Laboratory Biomarker Analysis	Patients received SD-QIV intramuscularly once at baseline (day 0) and again between 28-42 days later.

Primary Outcome Measures

Name	Time	Method
HD-TIV Compared With SD-QIV (Influenza A) - Immunogenicity	Visit 1 titers (baseline) were measured on day 0; visit 2 titers were measured 28-42 days after visit 1; visit 3 titers were measured 28-42 days after visit 2; and visit 4 titers were measured 138-222 days after visit 2.	Point estimates and 95% confidence intervals for proportion of subjects achieving seroprotection (≥1:40 HAI titer) and seroconversion (4-fold or greater rise in HAI titers from visit 1) for Influenza A antigens.

Secondary Outcome Measures

Name	Time	Method
Solicited Systemic Adverse Events	Adverse events were recorded for 7 days following each vaccination or until resolution, up to study conclusion.	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 systemic AEs included: fevers, fatigue/malaise, headache, nausea, body ache/myalgia, generally activity, and vomiting.
Percentage of Individuals in Each Group That Test Positive for Influenza by PCR	Nasal swabs were collected at each study visit or within 48 hours if a subject presented with influenza-like symptoms throughout the duration of the study.	The percentage of breakthrough flu in vaccinated participants, separated by treatment group.
HD-TIV Compared With SD-QIV (Influenza B) - Immunogenicity	Visit 1 titers (baseline) were measured on day 0; visit 2 titers were measured 28-42 days after visit 1; visit 3 titers were measured 28-42 days after visit 2; and visit 4 titers were measured 138-222 days after visit 2.	Point estimates and 95% confidence intervals for proportion of subjects achieving seroprotection (≥1:40 HAI titer) and seroconversion (4-fold or greater rise in HAI titers from visit 1) for Influenza B antigens.
Solicited Local Injection Site Adverse Events	Adverse events were recorded for 7 days following each vaccination or until resolution, up to study conclusion.	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."

Trial Locations

Locations (4): Northwestern University
🇺🇸
Chicago, Illinois, United States
Fred Hutchinson Cancer Center
🇺🇸
Seattle, Washington, United States
University of Alabama
🇺🇸
Birmingham, Alabama, United States
Vanderbilt-Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States