High Dose Influenza in Immunosuppressed Subjects
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 (by chance) assigned to receive 2 doses of either the standard licensed influenza vaccine or the experimental influenza vaccine. Participants will be asked to complete 5 study visits and 3 telephone contacts. Study procedures include blood draws. The duration of participation is about 6 months.
Biological: rHAO Trivalent Influenza Vaccine
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|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|
- 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. [ Time Frame: At Days 28 and 56 after the first vaccine dose. ] [ Designated as safety issue: No ]
- 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 ]
- 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 ]
- 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 ]
|Study Completion Date:||September 2010|
|Primary Completion Date:||September 2010 (Final data collection date for primary outcome measure)|
Active Comparator: TIV
50 subjects to receive 45 mcg of TIV administered on Day 0 and Day 28.
Standard trivalent influenza vaccine consisting of 15 mcg per antigen (45 mcg total) by intramuscular deltoid injection.
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.
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.
|United States, Texas|
|University of Texas MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|