Immunogenicity of Fluzone HD,A High Dose Influenza Vaccine, In Children With Cancer or HIV

Study Overview
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Brief Summary
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This is an open label-study of Fluzone HD, a high-dose form of trivalent, inactivated influenza vaccine (TIV), vs. Fluzone, a standard-dose form of TIV. Subjects with cancer or HIV will be vaccinated twice with one of the two vaccines and evaluated for development of immune responses.

Detailed Description
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The primary objectives of this study are to compare the immune response of Fluzone HD, a high-dose, trivalent influenza vaccine (TIV), to Fluzone, a standard-dose TIV, in children with cancer and in children with HIV. The secondary objectives of this study are to: Describe the safety and reactogenicity of high-dose and standard-dose TIV. Compare the immunogenicity induced by 1 dose, compared to 2 doses, of high-dose and standard-dose TIV. Describe the relationship between baseline lymphocyte numbers/function and robustness/durability of the immune response.

Official Title
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Immunogenicity of Fluzone HD,A High Dose Influenza Vaccine, In Children With Cancer or HIV

Conditions
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HIV, Cancer

Intervention / Treatment
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* Biological: Fluzone High Dose Vaccine
* Biological: Fluzone Standard Dose Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 3 years (on or past their 3rd birthday) through 21 years of age (not yet reached their 22nd birthday) at the time of entry into the study. Written informed consent (and assent, if applicable) obtained. Participant has a diagnosis of cancer or HIV. If subject has cancer, currently receiving chemotherapy and /or radiotherapy for the treatment of cancer or has received chemotherapy in the past 12 weeks Exclusion Criteria Severe hypersensitivity to egg proteins or any component of Fluzone, or life-threatening reactions after any previous administration of any influenza vaccine; History of Guillain-Barre´ syndrome in the subject or subject's family (parents, siblings, half siblings, or children); Not willing to agree to acceptable birth control for three months after study immunization

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Leukemia-HD<br>Subjects with a diagnosis of leukemia will be vaccinated twice with Fluzone High Dose Vaccine and evaluated for development of immune responses. | Biological: Fluzone High Dose Vaccine<br>* Two doses of Fluzone HD will be administered to children with leukemia, solid tumor, or HIV.<br>* Other names: Fluzone-HD;|
| Active Comparator: Leukemia-SD<br>Subjects with a diagnosis of leukemia will be vaccinated twice with Fluzone Standard Dose Vaccine and evaluated for development of immune responses. | Biological: Fluzone Standard Dose Vaccine<br>* Two doses of Fluzone Standard Dose Vaccine will be administered to children with leukemia, solid tumor, or HIV.<br>* Other names: Fluzone-SD;|
| Active Comparator: Solid Tumor-HD<br>Subjects with a diagnosis of solid tumor will be vaccinated twice with Fluzone High Dose Vaccine and evaluated for development of immune responses. | Biological: Fluzone High Dose Vaccine<br>* Two doses of Fluzone HD will be administered to children with leukemia, solid tumor, or HIV.<br>* Other names: Fluzone-HD;|
| Active Comparator: Solid Tumor-SD<br>Subjects with a diagnosis of solid tumor will be vaccinated twice with Fluzone Standard Dose Vaccine and evaluated for development of immune responses. | Biological: Fluzone Standard Dose Vaccine<br>* Two doses of Fluzone Standard Dose Vaccine will be administered to children with leukemia, solid tumor, or HIV.<br>* Other names: Fluzone-SD;|
| Active Comparator: HIV-HD<br>Subjects with a diagnosis of human immunodeficiency virus (HIV) will be vaccinated twice with Fluzone High Dose Vaccine and evaluated for development of immune responses. | Biological: Fluzone High Dose Vaccine<br>* Two doses of Fluzone HD will be administered to children with leukemia, solid tumor, or HIV.<br>* Other names: Fluzone-HD;|
| Active Comparator: HIV-SD<br>Subjects with a diagnosis of human immunodeficiency virus (HIV) will be vaccinated twice with Fluzone Standard Dose Vaccine and evaluated for development of immune responses. | Biological: Fluzone Standard Dose Vaccine<br>* Two doses of Fluzone Standard Dose Vaccine will be administered to children with leukemia, solid tumor, or HIV.<br>* Other names: Fluzone-SD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Seroconversion After 1 Dose of Vaccine | The immune response of Fluzone HD to Fluzone was determined using the hemagglutination-inhibition (HAI) assay to each of the 3 antigens contained in the vaccine: H1, H3 and B. Seroconversion was defined as a post-vaccine HAI titer ≥40 if baseline was <10, or a 4-fold rise in HAI titer if the baseline ≥10. | at least 21 days after first dose, which is given at the time of baseline evaluation visit, and prior to second dose | 
| Rate of Seroprotection After 1 Dose of Vaccine | The immune response of Fluzone HD to Fluzone was determined using the hemagglutination-inhibition (HAI) assay to each of the 3 antigens contained in the vaccine: H1, H3 and B. Seroprotection was defined as a post-vaccine HAI titer ≥40. | at least 21 days after first dose, which is given at the time of baseline evaluation visit, and prior to second dose | 
| Number of Participants Achieving Seroprotection After Second Dose of Vaccine | The immune response of Fluzone HD to Fluzone was determined using the hemagglutination-inhibition (HAI) assay to each of the 3 antigens contained in the vaccine: H1, H3 and B. Seroprotection was defined as a post-vaccine HAI titer ≥40. | 21 to 42 days after second dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Grade 3 and Grade 4 Adverse Events Possibly, Probably, or Definitely Attributable to Fluzone or Fluzone HD | Number of participants reporting grade 3 and grade 4 adverse events possibly, probably, or definitely attributable to Fluzone or Fluzone HD. | From initial vaccine administration through up to 8 months | 
| Rate of Sero-conversion for 1 Dose vs. 2 Doses of Fluzone HD | The rate of seroconversion to the 3 antigens contained in the vaccine was determined by hemagglutination-inhibition test and was compared by disease. The immune response of 1 dose vs. 2 doses of Fluzone HD was determined using the hemagglutination-inhibition (HAI) assay to each of the 3 antigens contained in the vaccine: H1, H3 and B. Seroconversion was defined as a post-vaccine HAI titer ≥40 if baseline was <10, or a 4-fold rise in HAI titer if the baseline ≥10. | at least 21 days after each dose of vaccine | 
| Rate of Sero-conversion for 1 Dose vs. 2 Doses of Fluzone SD | The rate of seroconversion to the 3 antigens contained in the vaccine was determined by hemagglutination-inhibition test and was compared by disease. The immune response of 1 dose vs. 2 doses of Fluzone SD was determined using the hemagglutination-inhibition (HAI) assay to each of the 3 antigens contained in the vaccine: H1, H3 and B. Seroconversion was defined as a post-vaccine HAI titer ≥40 if baseline was <10, or a 4-fold rise in HAI titer if the baseline ≥10. | at least 21 days after each dose of vaccine | 
| Rate of Vaccine Response by Seroconversion Compared by Absolute Lymphocyte Count (ALC) | The relationship between baseline lymphocyte numbers/function and robustness of the immune response will be described through descriptive analysis of relationships between pre-defined variables. | ALC at baseline and vaccine response at least 21 days after last dose of vaccine | 
| Rate of Vaccine Response by Seroprotection Compared by Absolute Lymphocyte Count (ALC) | The relationship between baseline lymphocyte numbers/function and robustness of the immune response will be described through descriptive analysis of relationships between pre-defined variables. | ALC at baseline and vaccine response at least 21 days after last dose of vaccine | 
| Number of Local Reactogenicity Events After First Dose | Number of moderate or greater local reactogenicity events associated with the administration of Fluzone or FluzoneHD. Local reactions were defined as pain, redness, or induration. | First 14 days after vaccination | 
| Number of Local Reactogenicity Events After Second Dose | Number of moderate or greater local reactogenicity events associated with the administration of Fluzone or FluzoneHD. Local reactions were defined as pain, redness, or induration. | First 14 days after vaccination | 
| Number of Systemic Reactogenicity Events After First Dose | Number of moderate or greater systemic reactogenicity event associated with the administration of Fluzone or FluzoneHD. Systemic reactions were defined as muscle ache, fatigue, or fever. | First 14 days after vaccination | 
| Number of Systemic Reactogenicity Events After Second Dose | Number of moderate or greater systemic reactogenicity event associated with the administration of Fluzone or FluzoneHD. Systemic reactions were defined as muscle ache, fatigue, or fever. | First 14 days after vaccination | 
| Comparison of Geometric Mean Titer (GMT) by HAI | Serum antibody levels expressed as the reciprocal of the dilution needed to inhibit hemagglutination in vitro. | Pre-vaccination, post-vaccination and 9 months after vaccination | 
| Comparison of Geometric Mean Ratios (GMR) by HAI | GMTs compared to each other as a ratio of the pre- and post-vaccine titers and as the ratio post-last dose to 9 months later. GMRs were compared pre- to post-vaccination and post- vaccination to 9 months later. | Pre-vaccination, post-vaccination and 9 months after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fluzone, Trivalent Influenza Vaccine