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

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.