High Dose Flu Vaccine in Treating Children Who Have Undergone Donor Stem Cell Transplant
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.
Inclusion Criteria
- Allogeneic HSCT recipients who are 3-35 months post-transplant
- Available for duration of study
- Patients with stable graft versus host disease (GVHD) for at least 4 weeks will be eligible (stable is defined as having no major increases in systemic immunosuppressive therapy for GVHD; adjustments of established medications to obtain a stable target level are acceptable and do not impact eligibility)
- Parent/legal guardian willing and capable of signing written informed consent
- Parent/legal guardian expected to be available for entire study
- Parent/legal guardian can be reached by telephone and/or electronic communication
- Subjects must have a platelet count of >= 30,000 to receive immunizations; patients requiring platelet transfusions are eligible to enroll and must have a platelet count >= 30,000 within 72 hours prior to their immunization, or platelet count >= 75,000 without transfusion documented within 30 days for subjects < 12 months post-transplant and within 90 days for subjects 12-35 months post-transplant
- CRITERIA FOR TEMPORARILY DELAYING VACCINE ADMINISTRATION
- Fever >= 100.4 degrees Fahrenheit (F)/38.0 degrees Celsius (C) (oral measurement), or an acute illness within 48 hours of enrollment
- Receipt of any live vaccines within four weeks or any inactivated vaccines within two weeks prior to potential study vaccination
- SUBJECTS WHO PARTICIPATED IN THE PREVIOUS INFLUENZA SEASON: Available for duration of study
- SUBJECTS WHO PARTICIPATED IN THE PREVIOUS INFLUENZA SEASON: Patients with stable GVHD for at least 4 weeks will be eligible (stable is defined as no major change in systemic immunosuppressive therapy for worsening GVHD; adjustment of actual dose to obtain a stable target level is acceptable)
- SUBJECTS WHO PARTICIPATED IN THE PREVIOUS INFLUENZA SEASON: Subjects must have a platelet count of >= 30,000 to receive the immunizations; patients requiring platelet transfusions are eligible to enroll and must have a platelet count >= 30,000 within 72 hours prior to their immunization, or platelet count >= 75,000 without transfusion documented within 30 days for subjects < 12 months post-transplant and within 90 days for subjects 12-35 months post-transplant
- SUBJECTS WHO PARTICIPATED IN THE PREVIOUS INFLUENZA SEASON: Parent/legal guardian willing and capable of signing written informed consent
- SUBJECTS WHO PARTICIPATED IN THE PREVIOUS INFLUENZA SEASON: Parent/legal guardian expected to be available for entire study
- SUBJECTS WHO PARTICIPATED IN THE PREVIOUS INFLUENZA SEASON: Parent/legal guardian can be reached by telephone and/or electronic communication
Exclusion Criteria
- History of hypersensitivity to previous influenza vaccination or severe hypersensitivity to eggs/egg protein
- History of Guillain-Barre syndrome
- Evidence of hematologic malignancy or disease relapse post-transplant (stable mixed chimerism is permitted)
- History of receiving current year seasonal influenza vaccine post-transplant
- Pregnant female
- History of proven influenza disease after September 1, 2018 prior to enrollment
- Non-allogeneic (e.g. autologous) or syngeneic hematopoietic stem cell transplant (SCT) recipients
- History of known active infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C
- History of known severe latex hypersensitivity
- Subjects who have received stem cell boost or delayed donor lymphocyte infusion within 90 days of enrollment, including day of enrollment
- Receipt of intravenous immunoglobulin (IVIG)/subcutaneous immunoglobulin (SCIG) < 27 days prior to calendar day of vaccination
- Subjects who have participated in year 1 and/or 2 of the study, and received study vaccine
- SUBJECTS WHO PARTICIPATED IN THE PREVIOUS INFLUENZA SEASON: History of hypersensitivity to previous influenza vaccination or severe hypersensitivity to eggs/egg protein
- SUBJECTS WHO PARTICIPATED IN THE PREVIOUS INFLUENZA SEASON: History of Guillain-Barre syndrome
- SUBJECTS WHO PARTICIPATED IN THE PREVIOUS INFLUENZA SEASON: Evidence of hematologic malignancy or disease relapse post-transplant (stable mixed chimerism is permitted)
- SUBJECTS WHO PARTICIPATED IN THE PREVIOUS INFLUENZA SEASON: History of receiving current year seasonal influenza vaccine post-transplant
- SUBJECTS WHO PARTICIPATED IN THE PREVIOUS INFLUENZA SEASON: Pregnant female
- SUBJECTS WHO PARTICIPATED IN THE PREVIOUS INFLUENZA SEASON: History of proven influenza disease after September 1, 2019 prior to enrollment
- SUBJECTS WHO PARTICIPATED IN THE PREVIOUS INFLUENZA SEASON: History of known active infection with HIV, hepatitis B or hepatitis C
- SUBJECTS WHO PARTICIPATED IN THE PREVIOUS INFLUENZA SEASON: Subjects who have received stem cell boost or delayed donor lymphocyte infusion within 90 days of enrollment, including day of enrollment
- SUBJECTS WHO PARTICIPATED IN THE PREVIOUS INFLUENZA SEASON: Receipt of IVIG/SCIG < 27 days prior to calendar day of vaccination
- SUBJECTS WHO PARTICIPATED IN THE PREVIOUS INFLUENZA SEASON: Non-allogeneic (e.g. autologous) or syngeneic hematopoietic SCT recipients
- SUBJECTS WHO PARTICIPATED IN THE PREVIOUS INFLUENZA SEASON: Subjects who have participated in year 1 and received study vaccine
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02860039.
PRIMARY OBJECTIVE:
I. To determine whether high-dose trivalent inactivated influenza vaccine (HD-TIV) compared with standard dose influenza vaccine (IV) 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 quadrivalent inactivated influenza vaccine (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/induration 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, ex-vivo T and B cell phenotype, and ex-vivo 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 (MN) responses.
VI. To compare the persistence of HAI and MN titers for all four antigen seven months after the last vaccine dose.
VII. To compare influenza detection by polymerase chain reaction (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 undergoing two consecutive years of vaccination using the same antigen dose.
IX. To evaluate neuraminidase inhibition titers (NAI) responses in children undergoing two consecutive years of vaccination and correlate them to HAI responses.
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 and 180 days.
Trial PhasePhase II
Trial Typeprevention
Lead OrganizationVanderbilt University/Ingram Cancer Center
Principal InvestigatorNatasha Halasa
- Primary IDVICCPED1647
- Secondary IDsNCI-2016-01090
- ClinicalTrials.gov IDNCT02860039