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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

Phase 2
18 Years
Not Enrolling

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Trial Information

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.

Inclusion Criteria:

- At least 18 years of age, between 6 and 12 months after undergoing their last
allogeneic donor hematopoietic stem cell transplantation with no or stable chronic
graft versus host disease (score 0-1).

- Underlying cancer is stable or in complete remission within 3 months prior to
enrollment as determined by the treating oncologist in written documentation stating
such fact.

- Ambulatory; community dwelling. Subjects will be considered ambulatory if they are
not institutionalized, bedridden or homebound.

- Able to return to the clinical site for reactogenicity examinations for at least 7
days after each injection.

- Patients with stable chronic viral infection [(other than Hepatitis B or C and human
immunodeficiency virus (HIV)]; any bacterial, mycobacterial or invasive fungal
infections that are on maintenance antimicrobial therapy are eligible. Antimicrobial
therapy includes: any antiviral, antibacterial or antifungal therapy use under the
standard guidelines for treatment or maintenance treatment of viral, bacterial or
invasive fungal infections.

- Women of childbearing potential (not surgically sterile or postmenopausal for greater
than or equal to 1 year) who are at risk of becoming pregnant must agree to practice
adequate contraception (i.e., barrier method, abstinence, or licensed hormonal
methods as recommended by her primary care provider) from at least 30 days prior to
enrollment and for at least 3 months after receipt of dose 2.

- Able to understand and comply with planned study procedures.

- Provides informed consent prior to initiation of any study procedures and is
available for all study visits.

Exclusion Criteria:

- Has moderate or severe chronic graft versus host disease (score 2-3) or uncontrolled
chronic graft-versus-host disease (GvHD).

- Has required high-dose corticosteroids: >16 mg prednisone or equivalent daily dose
(high-dose methylprednisolone, high-dose dexamethasone), or receiving
immunosuppressive agents such as tacrolimus, antithymocyte globulins, cyclosporine,
or methotrexate in past 4 weeks.

- Has long-term use (greater than 4 weeks) of moderate to high-dose inhaled steroids
(e.g., more than the equivalent of 264 mcg fluticasone; 600 mcg budesonide; 240 mcg
beclomethasone; 1000 mcg flunisolide, 750 mcg triamcinolone or 200 mcg mometasone, as
a daily dose) within 1 month prior to enrollment.

- Has received chemotherapy within the past 3 months for a refractory or relapsed

- Was given rituximab or ibritumomab tiuxetan in the past 6 months.

- Splenectomized individuals.

- Has a known allergy to eggs or other components of the vaccine (i.e., thimerosal) or
a severe reaction to influenza vaccine in the past.

- Has an acute or chronic condition or an acute change in a chronic condition that (in
the opinion of the investigator) would render vaccination unsafe or would interfere
with the evaluation of responses including but not limited to the following: acute
febrile illness, known chronic liver disease [history of increased alanine
transaminase (ALT) and aspartate aminotransferase (AST) levels in the past 4 weeks];
significant renal disease on dialysis; oxygen-dependent chronic lung disease, New
York Heart Association Functional Class III or IV; unstable or progressive neurologic
disorder; or uncontrolled diabetes mellitus. Medically unstable patients with
systolic blood pressure < 90 mmHg, pulse > 100 beats per minutes, or respiratory rate
of > 24 per minutes will not be included in this study.

- Has received immunoglobulin within 3 months or monoclonal antibodies within 4 weeks
prior to enrollment into the study.

- Has a history of Guillian-Barré Syndrome, vasovagal syncope, clinically symptomatic
pericardial effusion or cardiac tamponade, or Bell's palsy.

- Has an acute illness including an oral temperature greater than or equal to 100.0
degrees Fahrenheit, within one week prior to vaccination.

- Has a known history of human immunodeficiency virus (HIV) or Hepatitis B or Hepatitis
C. Screening for HIV will not be performed for this study.

- Has a positive urine pregnancy test prior to vaccination (if female of childbearing
potential), is breast-feeding, or has the intention to become pregnant within 3
months of receipt of their second dose of vaccine.

- Has received the current licensed trivalent influenza vaccine within the past 4

- Has received an investigational agent (drug, vaccine, biologic agent or a device)
within 4 weeks before vaccination, or expects to receive an experimental agent prior
to completing study visit 5.

- Has a diagnosis of schizophrenia, bipolar disease or other major psychiatric

- Has been hospitalized for psychiatric illness, history of suicide attempt or
confinement for danger to self or others.

- Is receiving psychiatric drugs (aripiprazole, clozapine, ziprasidone, haloperidol,
molindone, loxapine, thioridazine, thiothixene, pimozide, fluphenazine, risperidone,
mesoridazine, quetiapine, trifluoperazine, trifluopromazine, chlorprothixene,
chlorpromazine, perphenazine, olanzapine, carbamazepine, divalproex sodium, lithium
carbonate or lithium citrate). Subjects who are receiving a single antidepressant
drug and stable for at least 3 months prior to enrollment, without de-compensating
symptoms will be allowed to be enrolled in the study.

- Has any condition that would, in the opinion of the site investigator, place the
subject at an unacceptable risk of injury or render the subject unable to meet the
requirements of the protocol.

- Has any condition that the investigator believes may interfere with successful
completion of the study.

- Has a history of alcohol or drug abuse in the last 5 years.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Outcome Measure:

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.

Outcome Time Frame:

At Days 28 and 56 after the first vaccine dose.

Safety Issue:



United States: Federal Government

Study ID:




Start Date:

Completion Date:

September 2010

Related Keywords:

  • Influenza
  • Baculovirus, influenza, stem cell transplant
  • Influenza, Human



University of Texas MD Anderson Cancer Center Houston, Texas  77030