High Dose Flu Vaccine in Treating Children Who Have Undergone Donor Stem Cell Transplant
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.
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.
FOR YEAR 2:

 A. A target of at least 200 pediatric patients who received an allogeneic HSCT

 1. Inclusion criteria

 -  Allogeneic HSCT recipients who are 3-35 months post-transplant;

 -  3-17 years of age, inclusive;

 -  Available for duration of study;

 -  If patients are on immunosuppressive therapy for treatment of GVHD, then only
 those on stable doses for at least 4 weeks (or on tapering doses) will be
 eligible;

 -  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 or email.

 -  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.

 -  Recipients of CD34 selected grafts or other manipulated grafts (with any form of
 ex vivo T cell depletion) will be eligible to enroll if they have a CD3 count
 >100. (Please note: post-transplant cytoxan for haploidentical transplants is
 allowable).

 2. 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 chimerisms is permitted);

 -  History of receiving current year seasonal influenza vaccine influenza vaccine;

 -  Pregnant female;

 -  History of proven influenza disease after September 1, 2017

 -  Non-allogeneic (e.g. autologous) or syngeneic hematopoietic SCT recipients;

 -  History of known active infection with 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 IVIG <27 days prior to calendar day of vaccination Criteria for
 temporarily delaying vaccine administration: The following conditions are
 temporary or self-limiting, and a subject may be included in the study once the
 condition has resolved, provided that the subject is otherwise eligible: 1).
 Fever ≥100.4ºF/38.0ºC (oral measurement), or an acute illness within 48 hours of
 enrollment 2). Receipt of any live vaccines within four weeks or any inactivated
 vaccines within two weeks of study vaccination.

 B. For the 31 subjects enrolled in year 1, inclusion and exclusion criteria include:

 1. Inclusion criteria

 -  If patients are on immunosuppressive therapy for treatment of GVHD, then only
 those on stable doses for at least 4 weeks (or on tapering doses) will be
 eligible;

 -  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.

 -  Recipients of CD34 selected grafts or other manipulated grafts (with any form of
 ex vivo T cell depletion) will be eligible to enroll if they have a CD3 count
 >100. (Please note: post-transplant cytoxan for haploidentical transplants is
 allowable).

 2. Exclusion criteria

 -  Evidence of hematologic malignancy or disease relapse post-transplant (stable
 mixed chimerisms is permitted);

 -  History of receiving current year seasonal influenza vaccine influenza vaccine;

 -  Pregnant female;

 -  History of proven influenza disease after September 1, 2017

 -  History of known active infection with HIV, Hepatitis B or Hepatitis C;

 -  Subjects who have received stem cell boost or delayed donor lymphocyte infusion
 within 90 days of enrollment, including day of enrollment

 -  Receipt of IVIG <27 days prior to calendar day of vaccination

 Criteria for temporarily delaying vaccine administration: The following conditions are
 temporary or self-limiting, and a subject may be included in the study once the condition
 has resolved, provided that the subject is otherwise eligible: 1). Fever ≥100.4ºF/38.0ºC
 (oral measurement), or an acute illness within 48 hours of enrollment 2). Receipt of any
 live vaccines within four weeks or any inactivated vaccines within two weeks of study
 vaccination.