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High Dose Influenza in Immunosuppressed Subjects
This study is not yet open for participant recruitment.
Verified by National Institute of Allergy and Infectious Diseases (NIAID), November 2008
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00766285
  Purpose

Influenza is a common infection of the upper airways and lungs, and is caused by viruses. Cancer patients may need a stronger influenza vaccine than the general population to protect against influenza. The experimental vaccine is designed to be 9 times stronger than the standard vaccine, which may cause a stronger immune response against influenza in patients with a weakened immune system. The goal of this study is to compare the effects of a new experimental influenza vaccine to the effects of the standard influenza vaccine. One hundred bone marrow recipients, adult volunteers from the MD Anderson Cancer Center, 18 years of age or older, will participate in this study. They will be randomly assigned to receive 2 doses of either the standard licensed influenza vaccine or the experimental influenza vaccine. Participants will be asked to complete 3 study visits and two telephone contacts. Study procedures include blood draws. The duration of participation is about 6 months.


Condition Intervention Phase
Influenza
Biological: TIV
Biological: rHAO Trivalent Influenza Vaccine
Phase II

MedlinePlus related topics: Flu
Drug Information available for: Influenza Vaccines Fluvirin
U.S. FDA Resources
Study Type: Interventional
Study Design: Prevention, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title: 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

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • The frequency of four-fold or greater serum HAI and/or neutralization antibody rises in the two groups to the three HA types (H1, H3, and B) contained within the vaccine at Days 28 and 56 after the first vaccine dose. [ Time Frame: Blood for antibody tests will be drawn at Day 0, 28 and 56. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The frequencies and severity of solicited local and systemic adverse events in each vaccine dosage group. [ Time Frame: Day 0 through Day 7 following all vaccinations. ] [ Designated as safety issue: Yes ]
  • The geometric mean titer (GMT) of serum HAI and serum neutralizing antibody against the influenza A/H3N2, H1N1, and B virus. [ Time Frame: 1 month after each vaccination. ] [ Designated as safety issue: No ]
  • Adverse events (AE) or serious adverse events (SAE) information (solicited in-clinic and via memory aids and periodic targeted physical assessment). [ Time Frame: Duration of study. ] [ Designated as safety issue: Yes ]
  • The proportion of subjects in each vaccine dose group that achieves a HAI titer of at least 1:32. [ Time Frame: 28 days after the first and second dose of vaccine. ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Estimated Study Completion Date: December 2009
Estimated Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
TIV: Active Comparator
50 subjects to receive 45 mcg of TIV administered on Day 0 and Day 28.
Biological: TIV
Standard trivalent influenza vaccine consisting of 15 mcg per antigen (45 mcg total) by intramuscular deltoid injection.
rHAO: Experimental
50 subjects to receive 405 mcg of rHAO administered on Day 0 and Day 28.
Biological: rHAO Trivalent Influenza Vaccine
Trivalent rHAO vaccine consisting of 135 mcg per rHAO per 1 mL dose (405 mcg total) by intramuscular deltoid injection as determined by single radial immunodiffusion (SRID).

Detailed Description:

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 less than or equal to 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 objectives include determination of the safety and tolerability of a two-dose regimen of recombinant, baculovirus-expressed HA containing less than or equal to 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 transplantation, with no or stable 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 maintain a memory aid to record oral temperature and solicited systemic and local adverse events for 8 days (Day 0 through Day 7) after each immunization. Subjects will return to the clinic on Day 28 for adverse event (AE) and concomitant medication assessment, 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 vaccination. Participants will be involved in study related procedures for 6 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  • In partial or complete clinical remission of cancer, and determined to have no evidence of active disease following Hematopoietic stem cell transplantation (HSCT). Partial remission will be considered as patients who have received greater than 50 percent donor chimerism at 6 (plus/minus 1) month prior to enrollment, documented by bone marrow biopsy.
  • 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 HIV); any bacterial, mycobacterial or invasive fungal infections that are on maintenance antimicrobial therapy are eligible. Antimicrobial therapy include: 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 (grade 2-3) or uncontrolled chronic Graft-versus-host disease (GvHD).
  • Has required high-dose corticosteroids: >16mg prednisone or equivalent daily dose (high-dose methylprednisolone, high-dose dexamethasone, high-dose inhaled steroids), or receiving immunosuppressive agents such as tacrolimus, antithymocyte globulins, cyclosporine, or methotrexate in past 4 weeks.
  • Has received chemotherapy within the past 3 months for a refractory or relapsed cancer.
  • Was given rituximab (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 ALT and 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 < 70 mmHg, pulse > 140 beats per minutes, and respiratory rate of > 24 per minute will not be included in this study.
  • Receipt of this year's (2008-09) licensed influenza vaccine.
  • 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 100.4 degrees F, within one week prior to vaccination.
  • Has a known history of HIV and Hepatitis B or Hepatitis C. A 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.
  • 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 3.
  • Has a diagnosis of schizophrenia, bipolar disease or other major psychiatric diagnosis.
  • Has been hospitalized for psychiatric illness, history of suicide attempt or confinement for danger to self or others.
  • Is receiving psychiatric drugs. 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00766285

Contacts
Contact: Amar Safdar (713) 794-4450

Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
  More Information

Responsible Party: HHS/NIAID/DMID ( Robert Johnson )
Study ID Numbers: 06-0069
Study First Received: October 2, 2008
Last Updated: December 31, 2008
ClinicalTrials.gov Identifier: NCT00766285  
Health Authority: United States: Federal Government;   United States: Food and Drug Administration;   United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Baculovirus, influenza, stem cell transplant

Study placed in the following topic categories:
Virus Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Influenza, Human
Orthomyxoviridae Infections

Additional relevant MeSH terms:
RNA Virus Infections

ClinicalTrials.gov processed this record on January 16, 2009