Cancer, Influenza Viral Infections
Conditions
Keywords
Influenza vaccine, Oncology, Chemotherapy
Brief summary
The safety and immunogenicity of high dose influenza vaccine has not been studied in young patients receiving chemotherapy. This study will evaluate and compare the immunogenicity and safety of high dose influenza to standard dose influenza vaccine in adult oncology patients who are younger than 65 years old receiving chemotherapy.
Interventions
BIOLOGICALStandard Trivalent Influenza Vaccine
Each 0.5 mL dose contains influenza split virus antigens formulated to contain a total of 45 mcg of influenza virus hemagglutinin, 15 mcg each from the 3 influenza virus strains in the vaccine.One dose given per patient.
BIOLOGICALHigh-Dose Influenza Vaccine
Each 0.5 mL dose of Fluzone High-Dose contains influenza split virus antigens that are formulated to contain a total of 180 mcg of influenza virus hemagglutinin, 60 mcg each from the 3 influenza virus strains in the vaccine. One dose given per patient.
Sponsors
Sanofi
Saad Jamshed MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
1. 18 years old to less than 65 years old 2. Subjects with malignancy must be receiving chemotherapy 3. Medically stable 4. Able to understand and willingness to sign a written informed consent 5. Able to comply with study procedures 6. Life expectancy of more than 3 months 7. Adequate organ function: * ANC \>1000/mm3 * Platelet \>100,000/uL * Creatinine \<2 mg/dL * AST and ALT \<3 times the ULN
Exclusion criteria
1. Allergy to eggs 2. Prior allergy to Influenza Vaccine 3. History of Guillain-Barre Syndrome 4. Current febrile illness 5. Other immunosuppressive disease (recipients of solid organ transplant, uncontrolled HIV) 6. Autologous or Allogenic Stem Cell Transplant with in a year 7. Current immunotherapy or immunochemotherapy in the last 6 months (rituximab or ofatumumab)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Geometric Mean Titer (GMT) of High-dose Influenza Vaccine vs the Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Who Are Less Than 65 Years Old. | Baseline and 28 days | Measure Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) immunogenicity of high-dose (HD) and standard dose (SD) vaccine before and after vaccination at day 28. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Seroprotection Rate of High-dose Influenza Vaccine vs Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Less Than 65 Years Old. | 28 days | Seroprotection rate was defined as the percentage of patients with a HAI GMT of at least 1:40 28 days after vaccination. |
| The Seroconversion Rate of High-dose Influenza Vaccine Versus Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Less Than 65 Years Old. | Baseline and 28 days | Seroconversion rate was defined as the percentage of patients with a greater than or equal to 4-fold increase in HAI titer 28 days after vaccination. |
| Evaluate and Compare the Local Solicited Adverse Events to Both Vaccines. | 7 days | Local solicited adverse events, standard-dose (SD) vaccine and high-dose (HD) vaccine |
| Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | 7 days | Systemic solicited adverse events, standard-dose (SD) vaccine and high-dose (HD) vaccine |
| Evaluate and Compare the Local and Systemic Unsolicited Adverse Events to Both Vaccines. | 28 days | Unsolicited adverse events occurring in more than one patient, standard-dose (SD) vaccine and high-dose (HD) vaccine |
Countries
United States
Participant flow
Pre-assignment details
105 patients were enrolled but only 100 had evaluable data. 4 patients received a vaccination both in years 1 and 2 of the study- only year 1 results were included in the analysis. 1 additional patient was excluded from the efficacy analysis when it was revealed he had received a second vaccination in the same season.
Participants by arm
| Arm | Count |
|---|---|
| High-Dose Influenza Vaccine High-Dose Influenza Vaccine: Each 0.5 mL dose of Fluzone High-Dose contains influenza split virus antigens that are formulated to contain a total of 180 mcg of influenza virus hemagglutinin, 60 mcg each from the 3 influenza virus strains in the vaccine. One dose given per patient. | 50 |
| Standard Trivalent Influenza Vaccine Standard Trivalent Influenza Vaccine: Each 0.5 mL dose contains influenza split virus antigens formulated to contain a total of 45 mcg of influenza virus hemagglutinin, 15 mcg each from the 3 influenza virus strains in the vaccine.One dose given per patient. | 50 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Enrolled both years; year 1 data used | 4 | 0 |
| Overall Study | Received 2 doses of vaccine | 0 | 1 |
Baseline characteristics
| Characteristic | High-Dose Influenza Vaccine | Standard Trivalent Influenza Vaccine | Total |
|---|---|---|---|
| Age, Continuous | 53.94 years STANDARD_DEVIATION 7.16 | 52.9 years STANDARD_DEVIATION 7.95 | 53.4 years STANDARD_DEVIATION 7.54 |
| Region of Enrollment United States | 50 participants | 50 participants | 100 participants |
| Sex: Female, Male Female | 31 Participants | 26 Participants | 57 Participants |
| Sex: Female, Male Male | 19 Participants | 24 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 26 / 50 | 22 / 50 |
| serious Total, serious adverse events | 0 / 50 | 0 / 50 |
Outcome results
Primary
The Geometric Mean Titer (GMT) of High-dose Influenza Vaccine vs the Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Who Are Less Than 65 Years Old.
Measure Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) immunogenicity of high-dose (HD) and standard dose (SD) vaccine before and after vaccination at day 28.
Time frame: Baseline and 28 days
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| High-Dose Influenza Vaccine | The Geometric Mean Titer (GMT) of High-dose Influenza Vaccine vs the Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Who Are Less Than 65 Years Old. | Pre Vaccination H1N1 Antigen | 125.2 titers |
| High-Dose Influenza Vaccine | The Geometric Mean Titer (GMT) of High-dose Influenza Vaccine vs the Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Who Are Less Than 65 Years Old. | Pre Vaccination H3N2 Antigen | 134.1 titers |
| High-Dose Influenza Vaccine | The Geometric Mean Titer (GMT) of High-dose Influenza Vaccine vs the Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Who Are Less Than 65 Years Old. | Pre Vaccination B Antigen | 31.4 titers |
| High-Dose Influenza Vaccine | The Geometric Mean Titer (GMT) of High-dose Influenza Vaccine vs the Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Who Are Less Than 65 Years Old. | Post Vaccination H1N1 Antigen | 1350.1 titers |
| High-Dose Influenza Vaccine | The Geometric Mean Titer (GMT) of High-dose Influenza Vaccine vs the Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Who Are Less Than 65 Years Old. | Post Vaccination H3N2 Antigen | 1143.4 titers |
| High-Dose Influenza Vaccine | The Geometric Mean Titer (GMT) of High-dose Influenza Vaccine vs the Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Who Are Less Than 65 Years Old. | Post Vaccination B Antigen | 351.6 titers |
| Standard Trivalent Influenza Vaccine | The Geometric Mean Titer (GMT) of High-dose Influenza Vaccine vs the Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Who Are Less Than 65 Years Old. | Post Vaccination H3N2 Antigen | 811.2 titers |
| Standard Trivalent Influenza Vaccine | The Geometric Mean Titer (GMT) of High-dose Influenza Vaccine vs the Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Who Are Less Than 65 Years Old. | Pre Vaccination H1N1 Antigen | 266.1 titers |
| Standard Trivalent Influenza Vaccine | The Geometric Mean Titer (GMT) of High-dose Influenza Vaccine vs the Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Who Are Less Than 65 Years Old. | Post Vaccination H1N1 Antigen | 979.1 titers |
| Standard Trivalent Influenza Vaccine | The Geometric Mean Titer (GMT) of High-dose Influenza Vaccine vs the Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Who Are Less Than 65 Years Old. | Pre Vaccination H3N2 Antigen | 143.2 titers |
| Standard Trivalent Influenza Vaccine | The Geometric Mean Titer (GMT) of High-dose Influenza Vaccine vs the Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Who Are Less Than 65 Years Old. | Post Vaccination B Antigen | 228 titers |
| Standard Trivalent Influenza Vaccine | The Geometric Mean Titer (GMT) of High-dose Influenza Vaccine vs the Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Who Are Less Than 65 Years Old. | Pre Vaccination B Antigen | 54.7 titers |
Secondary
Evaluate and Compare the Local and Systemic Unsolicited Adverse Events to Both Vaccines.
Unsolicited adverse events occurring in more than one patient, standard-dose (SD) vaccine and high-dose (HD) vaccine
Time frame: 28 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High-Dose Influenza Vaccine | Evaluate and Compare the Local and Systemic Unsolicited Adverse Events to Both Vaccines. | Fatigue: Grade 1 or 2 | 6 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Local and Systemic Unsolicited Adverse Events to Both Vaccines. | Fatigue: Grade 3 | 1 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Local and Systemic Unsolicited Adverse Events to Both Vaccines. | Nausea: Grade 1 or 2 | 3 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Local and Systemic Unsolicited Adverse Events to Both Vaccines. | Nausea: Grade 3 | 1 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Local and Systemic Unsolicited Adverse Events to Both Vaccines. | Vomiting: Grade 1 or 2 | 2 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Local and Systemic Unsolicited Adverse Events to Both Vaccines. | Vomiting: Grade 3 | 1 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Local and Systemic Unsolicited Adverse Events to Both Vaccines. | Nausea: Grade 3 | 0 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Local and Systemic Unsolicited Adverse Events to Both Vaccines. | Fatigue: Grade 1 or 2 | 4 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Local and Systemic Unsolicited Adverse Events to Both Vaccines. | Vomiting: Grade 3 | 0 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Local and Systemic Unsolicited Adverse Events to Both Vaccines. | Fatigue: Grade 3 | 0 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Local and Systemic Unsolicited Adverse Events to Both Vaccines. | Vomiting: Grade 1 or 2 | 3 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Local and Systemic Unsolicited Adverse Events to Both Vaccines. | Nausea: Grade 1 or 2 | 11 participants |
Secondary
Evaluate and Compare the Local Solicited Adverse Events to Both Vaccines.
Local solicited adverse events, standard-dose (SD) vaccine and high-dose (HD) vaccine
Time frame: 7 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High-Dose Influenza Vaccine | Evaluate and Compare the Local Solicited Adverse Events to Both Vaccines. | Injection site pain- mild | 13 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Local Solicited Adverse Events to Both Vaccines. | Injection site pain-moderate | 3 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Local Solicited Adverse Events to Both Vaccines. | Injection site swelling-mild | 4 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Local Solicited Adverse Events to Both Vaccines. | Injection site swelling-moderate | 1 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Local Solicited Adverse Events to Both Vaccines. | Injection site redness-mild | 2 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Local Solicited Adverse Events to Both Vaccines. | Injection site redness-moderate | 1 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Local Solicited Adverse Events to Both Vaccines. | Injection site itching-mild | 4 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Local Solicited Adverse Events to Both Vaccines. | Injection site itching-moderate | 0 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Local Solicited Adverse Events to Both Vaccines. | Injection site itching-moderate | 0 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Local Solicited Adverse Events to Both Vaccines. | Injection site pain- mild | 10 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Local Solicited Adverse Events to Both Vaccines. | Injection site redness-mild | 2 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Local Solicited Adverse Events to Both Vaccines. | Injection site pain-moderate | 1 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Local Solicited Adverse Events to Both Vaccines. | Injection site itching-mild | 0 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Local Solicited Adverse Events to Both Vaccines. | Injection site swelling-mild | 2 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Local Solicited Adverse Events to Both Vaccines. | Injection site redness-moderate | 0 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Local Solicited Adverse Events to Both Vaccines. | Injection site swelling-moderate | 0 participants |
Secondary
Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines.
Systemic solicited adverse events, standard-dose (SD) vaccine and high-dose (HD) vaccine
Time frame: 7 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High-Dose Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Malaise-mild | 10 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Fever-severe | 0 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Malaise-moderate | 10 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Fever-mild | 2 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Malaise-severe | 6 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Headache-moderate | 6 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Myalgia-mild | 12 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Headache-mild | 9 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Myalgia-moderate | 8 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Headache-severe | 1 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Myalgia-severe | 2 participants |
| High-Dose Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Fever-moderate | 1 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Myalgia-severe | 1 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Fever-mild | 1 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Fever-moderate | 1 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Headache-mild | 12 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Headache-moderate | 4 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Headache-severe | 0 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Malaise-mild | 13 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Malaise-moderate | 6 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Malaise-severe | 3 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Myalgia-mild | 12 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Myalgia-moderate | 3 participants |
| Standard Trivalent Influenza Vaccine | Evaluate and Compare the Systemic Solicited Adverse Events to Both Vaccines. | Fever-severe | 0 participants |
Secondary
The Seroconversion Rate of High-dose Influenza Vaccine Versus Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Less Than 65 Years Old.
Seroconversion rate was defined as the percentage of patients with a greater than or equal to 4-fold increase in HAI titer 28 days after vaccination.
Time frame: Baseline and 28 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High-Dose Influenza Vaccine | The Seroconversion Rate of High-dose Influenza Vaccine Versus Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Less Than 65 Years Old. | H1N1 Antigen | 72 percentage of participants |
| High-Dose Influenza Vaccine | The Seroconversion Rate of High-dose Influenza Vaccine Versus Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Less Than 65 Years Old. | H3N2 Antigen | 80 percentage of participants |
| High-Dose Influenza Vaccine | The Seroconversion Rate of High-dose Influenza Vaccine Versus Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Less Than 65 Years Old. | B Antigen | 80 percentage of participants |
| Standard Trivalent Influenza Vaccine | The Seroconversion Rate of High-dose Influenza Vaccine Versus Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Less Than 65 Years Old. | H1N1 Antigen | 46 percentage of participants |
| Standard Trivalent Influenza Vaccine | The Seroconversion Rate of High-dose Influenza Vaccine Versus Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Less Than 65 Years Old. | H3N2 Antigen | 58 percentage of participants |
| Standard Trivalent Influenza Vaccine | The Seroconversion Rate of High-dose Influenza Vaccine Versus Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Less Than 65 Years Old. | B Antigen | 44 percentage of participants |
Secondary
The Seroprotection Rate of High-dose Influenza Vaccine vs Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Less Than 65 Years Old.
Seroprotection rate was defined as the percentage of patients with a HAI GMT of at least 1:40 28 days after vaccination.
Time frame: 28 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High-Dose Influenza Vaccine | The Seroprotection Rate of High-dose Influenza Vaccine vs Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Less Than 65 Years Old. | H1N1 Antigen | 96 percentage of participants |
| High-Dose Influenza Vaccine | The Seroprotection Rate of High-dose Influenza Vaccine vs Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Less Than 65 Years Old. | H3N2 Antigen | 96 percentage of participants |
| High-Dose Influenza Vaccine | The Seroprotection Rate of High-dose Influenza Vaccine vs Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Less Than 65 Years Old. | B Antigen | 88 percentage of participants |
| Standard Trivalent Influenza Vaccine | The Seroprotection Rate of High-dose Influenza Vaccine vs Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Less Than 65 Years Old. | H1N1 Antigen | 90 percentage of participants |
| Standard Trivalent Influenza Vaccine | The Seroprotection Rate of High-dose Influenza Vaccine vs Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Less Than 65 Years Old. | H3N2 Antigen | 96 percentage of participants |
| Standard Trivalent Influenza Vaccine | The Seroprotection Rate of High-dose Influenza Vaccine vs Standard Trivalent Influenza Vaccine in Adult Subjects on Chemotherapy Less Than 65 Years Old. | B Antigen | 72 percentage of participants |