Pediatric Patients With Acute Lymphoblastic Leukemia
Conditions
Brief summary
This is a phase I safety and immunogenicity trial comparing high-dose (HD)trivalent inactivated influenza vaccine (TIV) to standard dose (SD) TIV in pediatric patients with Acute Lymphoblastic Leukemia.
Interventions
0.5 mL of high-dose trivalent inactivated influenza vaccine, either one dose or 2 based on whether the patient has previously received standard dose trivalent inactivated influenza vaccine.
0.5 mL standard dose trivalent inactivated influenza vaccine
Sponsors
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Pediatric patients with standard or high risk Acute Lymphoblastic Leukemia. * Must be in 1st complete remission. * Must be 4 weeks into maintenance therapy. * 17 years of age, inclusive. * Available for duration of study.
Exclusion criteria
* History of hypersensitivity to previous influenza vaccination or hypersensitivity to eggs/egg protein. * History of Guillain-Barre syndrome. * Evidence of relapsed disease. * Have any condition that would, in the opinion of the site investigator, place them at an unacceptable risk of injury or render them unable to meet the requirements of the protocol. * Have any condition that the investigator believes may interfere with successful completion of the study. * History of receiving 2010 - 2011 influenza vaccine. * Pregnant female. * History of proven influenza disease after September 1, 2010.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Local Reactions After Each Vaccination | From baseline to 7 days after each vaccination | Number of participants with local reactions after each vaccination |
| Systemic Reaction | From baseline to 7 days after each vaccination | Number of participants with systemic reactions after each vaccination |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity: Number of Participants With a Post-titer ≥1:40 | About 6 months after last dose of vaccine. | Post-titer ≥1:40 for three strains (A/California/7/09/H1N1, A/Perth/16/2009/ H3N2, B/Brisbane/60/2008) |
| Immunogenicity: Number of Participants With a Post-titer Greater Than or Equal to a Fourfold Titer Rise | About 6 months after last dose of vaccine. | Greater than or equal to a Fourfold titer rise three strains (A/California/7/09/H1N1, A/Perth/16/2009/ H3N2, B/Brisbane/60/2008) |
| Immunogenicity: Geometric Mean Titers Post-vaccine in Study Participants | About 6 months after last dose of vaccine. | Geometric mean titers post-vaccine (A/California/7/09/H1N1, A/Perth/16/2009/ H3N2, B/Brisbane/60/2008) |
| Immunogenicity: The Geometric Mean Titers Pre-vaccine in Study Participants | baseline | Geometric mean titers pre-vaccine (A/California/7/09/H1N1, A/Perth/16/2009/ H3N2, B/Brisbane/60/2008) |
| Immunogenicity:Number of Participants With a Pre-titer ≥1:40 | About 6 months after last dose of vaccine. | Pre-titer ≥1:40 for three strains (A/California/7/09/H1N1, A/Perth/16/2009/ H3N2, B/Brisbane/60/2008) |
Countries
United States
Participant flow
Pre-assignment details
Four subjects (from the high dose group) were excluded from the data analysis , because they were given the second dose of TIV outside the study window period. These four subjects were included in the adverse event reporting.
Participants by arm
| Arm | Count |
|---|---|
| High-Dose Trivalent Inactivated Influenza Vaccine 0.5 mL of high-dose trivalent inactivated influenza vaccine, either one dose or 2 based on whether the patient has previously received standard dose trivalent inactivated influenza vaccine.
High-dose trivalent inactivated influenza vaccine: 0.5 mL of high-dose trivalent inactivated influenza vaccine, either one dose or 2 based on whether the patient has previously received standard dose trivalent inactivated influenza vaccine. | 30 |
| Standard Dose Trivalent Inactivated Influenza Vaccine 0.5 mL standard dose trivalent inactivated influenza vaccine, either one dose or 2 based on whether the patient has previously received standard dose trivalent inactivated influenza vaccine
Standard dose trivalent inactivated influenza vaccine: 0.5 mL standard dose trivalent inactivated influenza vaccine | 16 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 4 | 0 |
Baseline characteristics
| Characteristic | High-Dose Trivalent Inactivated Influenza Vaccine | Standard Dose Trivalent Inactivated Influenza Vaccine | Total |
|---|---|---|---|
| Age, Customized <=18 years | 30 Participants | 16 Participants | 46 Participants |
| Age, Customized >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 28 Participants | 12 Participants | 40 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 27 Participants | 12 Participants | 39 Participants |
| Region of Enrollment United States | 30 participants | 16 participants | 46 participants |
| Sex/Gender, Customized Female | 12 Participants | 5 Participants | 17 Participants |
| Sex/Gender, Customized Male | 18 Participants | 11 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 16 |
| other Total, other adverse events | 21 / 34 | 14 / 16 |
| serious Total, serious adverse events | 9 / 34 | 6 / 16 |
Outcome results
Primary
Local Reactions After Each Vaccination
Number of participants with local reactions after each vaccination
Time frame: From baseline to 7 days after each vaccination
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-Dose Trivalent Inactivated Influenza Vaccine | Local Reactions After Each Vaccination | Pain | 12 Participants |
| High-Dose Trivalent Inactivated Influenza Vaccine | Local Reactions After Each Vaccination | Tenderness | 14 Participants |
| High-Dose Trivalent Inactivated Influenza Vaccine | Local Reactions After Each Vaccination | Intense Swelling | 3 Participants |
| High-Dose Trivalent Inactivated Influenza Vaccine | Local Reactions After Each Vaccination | Redness | 4 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Local Reactions After Each Vaccination | Redness | 2 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Local Reactions After Each Vaccination | Pain | 7 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Local Reactions After Each Vaccination | Intense Swelling | 3 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Local Reactions After Each Vaccination | Tenderness | 9 Participants |
Primary
Systemic Reaction
Number of participants with systemic reactions after each vaccination
Time frame: From baseline to 7 days after each vaccination
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-Dose Trivalent Inactivated Influenza Vaccine | Systemic Reaction | Fever | 4 Participants |
| High-Dose Trivalent Inactivated Influenza Vaccine | Systemic Reaction | Nausea | 7 Participants |
| High-Dose Trivalent Inactivated Influenza Vaccine | Systemic Reaction | Decrease in Activity | 13 Participants |
| High-Dose Trivalent Inactivated Influenza Vaccine | Systemic Reaction | Body aches | 6 Participants |
| High-Dose Trivalent Inactivated Influenza Vaccine | Systemic Reaction | Headache | 6 Participants |
| High-Dose Trivalent Inactivated Influenza Vaccine | Systemic Reaction | Vomiting | 2 Participants |
| High-Dose Trivalent Inactivated Influenza Vaccine | Systemic Reaction | Fatigue | 14 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Systemic Reaction | Vomiting | 7 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Systemic Reaction | Fatigue | 14 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Systemic Reaction | Decrease in Activity | 7 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Systemic Reaction | Fever | 3 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Systemic Reaction | Headache | 9 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Systemic Reaction | Nausea | 6 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Systemic Reaction | Body aches | 3 Participants |
Secondary
Immunogenicity: Geometric Mean Titers Post-vaccine in Study Participants
Geometric mean titers post-vaccine (A/California/7/09/H1N1, A/Perth/16/2009/ H3N2, B/Brisbane/60/2008)
Time frame: About 6 months after last dose of vaccine.
Population: Participants that receive only 1 dose of vaccine. In addition, two subjects were excluded due to lack of complete immunogenicity data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| High-Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: Geometric Mean Titers Post-vaccine in Study Participants | A/Perth/16/2009 H3N2 | 62.9 Titers |
| High-Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: Geometric Mean Titers Post-vaccine in Study Participants | A/California/7/09 H1N1 | 97.9 Titers |
| High-Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: Geometric Mean Titers Post-vaccine in Study Participants | B/Brisbane/60/2008 | 74.4 Titers |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: Geometric Mean Titers Post-vaccine in Study Participants | A/Perth/16/2009 H3N2 | 76.5 Titers |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: Geometric Mean Titers Post-vaccine in Study Participants | A/California/7/09 H1N1 | 322.9 Titers |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: Geometric Mean Titers Post-vaccine in Study Participants | B/Brisbane/60/2008 | 50.6 Titers |
Secondary
Immunogenicity: Number of Participants With a Post-titer ≥1:40
Post-titer ≥1:40 for three strains (A/California/7/09/H1N1, A/Perth/16/2009/ H3N2, B/Brisbane/60/2008)
Time frame: About 6 months after last dose of vaccine.
Population: Participants that receive only 1 dose of vaccine. In addition, two subjects were excluded due to lack of complete immunogenicity data
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: Number of Participants With a Post-titer ≥1:40 | A/California/7/09 H1N1 | 20 Participants |
| High-Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: Number of Participants With a Post-titer ≥1:40 | A/Perth/16/2009 H3N2 | 13 Participants |
| High-Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: Number of Participants With a Post-titer ≥1:40 | B/Brisbane/60/2008 | 19 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: Number of Participants With a Post-titer ≥1:40 | A/California/7/09 H1N1 | 11 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: Number of Participants With a Post-titer ≥1:40 | A/Perth/16/2009 H3N2 | 8 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: Number of Participants With a Post-titer ≥1:40 | B/Brisbane/60/2008 | 9 Participants |
Secondary
Immunogenicity: Number of Participants With a Post-titer Greater Than or Equal to a Fourfold Titer Rise
Greater than or equal to a Fourfold titer rise three strains (A/California/7/09/H1N1, A/Perth/16/2009/ H3N2, B/Brisbane/60/2008)
Time frame: About 6 months after last dose of vaccine.
Population: Participants that receive only 1 dose of vaccine. In addition, two subjects were excluded due to lack of complete immunogenicity data
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: Number of Participants With a Post-titer Greater Than or Equal to a Fourfold Titer Rise | A/California/7/09 H1N1 | 6 Participants |
| High-Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: Number of Participants With a Post-titer Greater Than or Equal to a Fourfold Titer Rise | A/Perth/16/2009 H3N2 | 8 Participants |
| High-Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: Number of Participants With a Post-titer Greater Than or Equal to a Fourfold Titer Rise | B/Brisbane/60/2008 | 2 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: Number of Participants With a Post-titer Greater Than or Equal to a Fourfold Titer Rise | A/California/7/09 H1N1 | 6 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: Number of Participants With a Post-titer Greater Than or Equal to a Fourfold Titer Rise | A/Perth/16/2009 H3N2 | 5 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: Number of Participants With a Post-titer Greater Than or Equal to a Fourfold Titer Rise | B/Brisbane/60/2008 | 0 Participants |
Secondary
Immunogenicity:Number of Participants With a Pre-titer ≥1:40
Pre-titer ≥1:40 for three strains (A/California/7/09/H1N1, A/Perth/16/2009/ H3N2, B/Brisbane/60/2008)
Time frame: About 6 months after last dose of vaccine.
Population: Participants that receive only 1 dose of vaccine. In addition, two subjects were excluded due to lack of complete immunogenicity data
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity:Number of Participants With a Pre-titer ≥1:40 | A/California/7/09 H1N1 | 17 Participants |
| High-Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity:Number of Participants With a Pre-titer ≥1:40 | A/Perth/16/2009 H3N2 | 9 Participants |
| High-Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity:Number of Participants With a Pre-titer ≥1:40 | B/Brisbane/60/2008 | 21 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity:Number of Participants With a Pre-titer ≥1:40 | A/California/7/09 H1N1 | 9 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity:Number of Participants With a Pre-titer ≥1:40 | A/Perth/16/2009 H3N2 | 7 Participants |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity:Number of Participants With a Pre-titer ≥1:40 | B/Brisbane/60/2008 | 11 Participants |
Secondary
Immunogenicity: The Geometric Mean Titers Pre-vaccine in Study Participants
Geometric mean titers pre-vaccine (A/California/7/09/H1N1, A/Perth/16/2009/ H3N2, B/Brisbane/60/2008)
Time frame: baseline
Population: Participants that receive only 1 dose of vaccine. In addition, two subjects were excluded due to lack of complete immunogenicity data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| High-Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: The Geometric Mean Titers Pre-vaccine in Study Participants | A/California/7/09 H1N1 | 46.2 Titers |
| High-Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: The Geometric Mean Titers Pre-vaccine in Study Participants | A/Perth/16/2009 H3N2 | 28.3 Titers |
| High-Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: The Geometric Mean Titers Pre-vaccine in Study Participants | B/Brisbane/60/2008 | 66.5 Titers |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: The Geometric Mean Titers Pre-vaccine in Study Participants | A/California/7/09 H1N1 | 87.4 Titers |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: The Geometric Mean Titers Pre-vaccine in Study Participants | A/Perth/16/2009 H3N2 | 28.8 Titers |
| Standard Dose Trivalent Inactivated Influenza Vaccine | Immunogenicity: The Geometric Mean Titers Pre-vaccine in Study Participants | B/Brisbane/60/2008 | 56.1 Titers |