Safety and Immunogenicity of High Dose Baculovirus-Expressed Recombinant Trivalent HA Influenza Vaccine in Adult Recipients of Allogeneic Hematopoietic Stem Cell Transplantation: Phase II Double-Blind Trial
Bone marrow transplantation (BMT) patients are immunocompromised to a varying degree
depending upon genetic relationship between donor and recipient with compromising therapy
required for allogeneic transplants. Responses to influenza vaccine in this population have
been poor and yet influenza virus infection can lead to serious disease. There is a need for
prophylaxis against influenza in this population. One approach to improving immune responses
to influenza vaccines in BMT patients could be to increase dosage and number of doses of
vaccine. This approach has increased responses in a variety of populations. Moreover, using
purified hemagglutinin (HA) vaccines in the form of rDNA-expressed HA protein in a
baculovirus expression system has increased immune responses without an increase in
reactogenicity. Researchers hypothesize that an increased dosage and 2 doses of a purified
influenza vaccine will increase serum hemagglutination inhibition (HAI) and neutralizing
antibody responses significantly over those following 2 doses of conventional vaccine in BMT
patients. The primary objective of this study is to determine if 2 doses of a
baculovirus-expressed recombinant trivalent influenza vaccine containing approximately 135
mcg per HA results in a significantly higher proportion of subjects achieving a Day 28 and
Day 56 post vaccination increase in serum HAI and neutralizing antibody titer than seen
after immunization with standard dose licensed trivalent inactivated influenza vaccine in
immunosuppressed allogeneic HSCT (hematopoietic stem cell transplantation) recipients. The
secondary objective is determination of the safety and tolerability of a two-dose regimen of
recombinant, baculovirus-expressed HA containing approximately 135 mcg per HA administered
by intramuscular injection to patients following allogeneic HSCT, and comparison of the
geometric mean titers (GMT) of serum HAI and neutralizing antibody against all 3 virus
strains contained in the vaccine. The study will enroll 100 adult (greater than or equal to
18 years of age) allogeneic HSCT recipients between 6 and 12 months following bone marrow
transplantation, with no or stable chronic graft-versus-host disease, who are evaluated at
the outpatient BMT clinic at M.D. Anderson Cancer Center. Subjects will be randomized to
receive either licensed trivalent inactivated influenza vaccine (TIV) or
baculovirus-expressed recombinant trivalent hemagglutinin vaccine (rHA0). All injections
will be administered into the deltoid muscle. Subjects will be randomized (50 per group) to
receive a vaccination on Day 0 and a second dose 4 weeks later. Subjects will be observed in
the clinic for at least 20 minutes after inoculation, and subjects will maintain a memory
aid to record oral temperature and solicited systemic and local adverse events (AE)s for 8
days (Day 0 through Day 7) after each immunization. Subjects will be seen on Day 2 and Day
30 (1-5 days after each vaccination) for an arm check, vital signs, assessment of possible
AEs, concomitant medication assessment, and a targeted physical examination if indicated.
Subjects will be contacted by phone on Day 8 and Day 36 (7-10 days after each vaccination)
to review the memory aid and to assess for possible AEs or serious (S) AEs. Subjects will
return to the clinic on Day 28 for AE and concomitant medication assessment, a targeted
physical examination if indicated, and a review of the memory aid prior to receiving the
second dose of vaccine. Serum for vaccine immunogenicity evaluations will be collected prior
to vaccination at Days 0 and 28, and 56 days after the first vaccine dose. Participants will
be involved in study related procedures for 6 months.
Interventional
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Frequency of four-fold or greater serum hemagglutination inhibition (HAI) and/or neutralization antibody rises in the 2 groups to the 3 hemagglutinin (HA) types (H1, H3, and B) contained within the vaccine.
At Days 28 and 56 after the first vaccine dose.
No
United States: Federal Government
06-0069
NCT00766285
September 2010
Name | Location |
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University of Texas MD Anderson Cancer Center | Houston, Texas 77030 |