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

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.

Inclusion Criteria:

- Allogeneic HSCT recipients who are 3-23 months post-transplant

- Available for duration of study

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

- 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; for subjects <
12 months post-transplant, if a platelet count of >= 75,000 is documented without
transfusion support within 14 days of the immunization, then an additional platelet
count does not need to be repeated prior to immunization; for subjects 12-23 months
post-transplant, if a platelet count of >= 75,000 is documented without transfusion
support within 90 days of the immunization, then an additional platelet count does not
need to be repeated prior to immunization

Exclusion Criteria:

- History of hypersensitivity to previous influenza vaccination or severe or moderate
hypersensitivity to eggs/egg protein

- History of Guillain-Barre syndrome

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

- History of receiving 2017-2018 influenza vaccine

- Pregnant female

- History of proven influenza disease after September 1, 2017

- 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 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 therapy (IVIG) < 27 days prior to vaccination

- CD34 selection or total cell depletion outside haploidentical transplants