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

Phase 2

Completed

Conditions: HIV
Cancer

Interventions: Biological: Fluzone Standard Dose Vaccine
Biological: Fluzone High Dose Vaccine

Registration Number: NCT01205581

Lead Sponsor: St. Jude Children's Research Hospital

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 85

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HIV-SD	Fluzone Standard Dose Vaccine	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.
HIV-HD	Fluzone High Dose Vaccine	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.
Leukemia-HD	Fluzone High Dose Vaccine	Subjects with a diagnosis of leukemia will be vaccinated twice with Fluzone High Dose Vaccine and evaluated for development of immune responses.
Leukemia-SD	Fluzone Standard Dose Vaccine	Subjects with a diagnosis of leukemia will be vaccinated twice with Fluzone Standard Dose Vaccine and evaluated for development of immune responses.
Solid Tumor-HD	Fluzone High Dose Vaccine	Subjects with a diagnosis of solid tumor will be vaccinated twice with Fluzone High Dose Vaccine and evaluated for development of immune responses.
Solid Tumor-SD	Fluzone Standard Dose Vaccine	Subjects with a diagnosis of solid tumor will be vaccinated twice with Fluzone Standard Dose Vaccine and evaluated for development of immune responses.

Primary Outcome Measures

Name	Time	Method
Rate of Seroprotection After 1 Dose of Vaccine	at least 21 days after first dose, which is given at the time of baseline evaluation visit, and prior to second dose	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.
Number of Participants Achieving Seroprotection After Second Dose of Vaccine	21 to 42 days after second dose	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.
Rate of Seroconversion After 1 Dose of Vaccine	at least 21 days after first dose, which is given at the time of baseline evaluation visit, and prior to second dose	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.

Secondary Outcome Measures

Name	Time	Method
Number of Systemic Reactogenicity Events After First Dose	First 14 days after vaccination	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.
Comparison of Geometric Mean Titer (GMT) by HAI	Pre-vaccination, post-vaccination and 9 months after vaccination	Serum antibody levels expressed as the reciprocal of the dilution needed to inhibit hemagglutination in vitro.
Rate of Vaccine Response by Seroconversion Compared by Absolute Lymphocyte Count (ALC)	ALC at baseline and vaccine response at least 21 days after last dose of vaccine	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.
Number of Local Reactogenicity Events After First Dose	First 14 days after vaccination	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.
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	Number of participants reporting grade 3 and grade 4 adverse events possibly, probably, or definitely attributable to Fluzone or Fluzone HD.
Rate of Sero-conversion for 1 Dose vs. 2 Doses of Fluzone HD	at least 21 days after each dose of vaccine	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.
Rate of Vaccine Response by Seroprotection Compared by Absolute Lymphocyte Count (ALC)	ALC at baseline and vaccine response at least 21 days after last dose of vaccine	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.
Rate of Sero-conversion for 1 Dose vs. 2 Doses of Fluzone SD	at least 21 days after each dose of vaccine	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.
Number of Local Reactogenicity Events After Second Dose	First 14 days after vaccination	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.
Number of Systemic Reactogenicity Events After Second Dose	First 14 days after vaccination	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.
Comparison of Geometric Mean Ratios (GMR) by HAI	Pre-vaccination, post-vaccination and 9 months after vaccination	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.