Evaluation of Antibody Response to High-Dose Seasonal Influenza Vaccination in Patients With Myeloid Malignancy Receiving Chemotherapy and Healthy Volunteers
Primary Purpose
Acute Myeloid Leukemia, Myelodysplastic Syndrome
Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Trivalent Influenza Vaccine
Sponsored by
About this trial
This is an interventional supportive care trial for Acute Myeloid Leukemia
Eligibility Criteria
Inclusion Criteria:
- Subject or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to undergoing any investigational biospecimen (blood) collection procedure
- Willing to undergo seasonal influenza vaccination with Fluzone high dose at Roswell Park Cancer Institute within 2 weeks of enrollment of this study
- Estimated survival of 8 weeks or more following enrollment on the study
Exclusion Criteria:
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active influenza infection or influenza-like-illness
- Women who are attempting pregnancy or known to be pregnant by clinical history or nursing female subjects
- Unwilling or unable to follow protocol requirements
- Use of prednisone > 10 mg/day (or its equivalent for other steroids) for > 2 weeks immediately prior to receiving seasonal influenza vaccination
- Received dose of seasonal influenza vaccination prior to enrollment
- Participation at the time of study enrollment in another clinical trial investigating immunotherapeutic agents (like anti-PD1 or anti-PDL1 or anti-CTLA4 antibodies or vaccines); concurrent participation in an observational/non-interventional study or an interventional study investigating tyrosine kinase inhibitor or other targeted agents use is acceptable
- Inability to receive seasonal influenza vaccine due to prior hypersensitivity to eggs, chicken proteins, or any of the vaccine components
- History of a life-threatening reaction to influenza vaccination or to a vaccine containing similar substances
- Personal history of Guillain-Barre syndrome
- Any condition which in the investigator's opinion deems the subject an unsuitable candidate to receive annual influenza vaccination or may potentially affect the response to influenza vaccination
- Adults unable to consent, individuals who are not yet adults (infants, children, and teenagers), women who are known to be pregnant, attempting pregnancy, or nursing women, and prisoners will be excluded from the study
Sites / Locations
- Roswell Park Cancer Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Supportive Care (trivalent influenza vaccine)
Arm Description
Within 14 days of baseline influenza titer, patients receive trivalent influenza vaccine IM on day 0 (patients in cohorts 1 and 5 receive the vaccine at any time, patients in cohorts 2 and 3 receive the vaccine between days 14-25 of hypomethylating agent therapy course, and patients in cohort 4 receive the vaccine between days 21-365 from onset of cytotoxic chemotherapy). Patients then undergo titer assessment at days 25-90 and days 115-185.
Outcomes
Primary Outcome Measures
Antibody response (by microneutralization assay) to influenza vaccination
The geometric mean (GMT) and standard deviation of antibody titers will be calculated by cohort at the baseline assessment and 1-3 months post vaccination time points. Antibody response is assessed using the outcome measures: seroprotection, seroconversion, and GMT. Seroprotection is defined as an hemagglutination inhibition (HAI) titer >= 1:40 of each individual influenza antigen. Seroconversion is defined as >= 4-fold increase in post-vaccination titer of each individual influenza antigen. The seroprotection and seroconversion rates will be reported by age strata, cohort, and time-point (1-3 months and 4-6 months post vaccination) using 95% confidence intervals obtained using Jeffrey's prior method. The GMT at each time-point will be compared using one-sided permutation T-tests about the log-transformed data. The GMT ratio (GMTR) between 1-3 months post vaccination and baseline will also be calculated and reported by cohort using a 95% confidence interval.
Secondary Outcome Measures
T-cell subset population assessed using flow cytometry
T-cell subset populations will be correlated with antibody responses to influenza vaccination. Blood samples will be collected and stored at different time-points for assessment of T-cell response to influenza vaccination using influenza specific tetramer staining by flow cytometry. The seroprotection and seroconversion rates will be reported by cohort and time-point (1-3 months and 4-6 months post vaccination) using 95% confidence intervals obtained using Jeffrey's prior method. The rates will be compared between the lenalidomide and healthy control cohorts using one-sided Barnard's tests. The GMTR between 1-3 months post vaccination and baseline will also be calculated and reported by cohort using a 95% confidence interval.
Full Information
NCT ID
NCT04484532
First Posted
July 20, 2020
Last Updated
June 2, 2023
Sponsor
Roswell Park Cancer Institute
1. Study Identification
Unique Protocol Identification Number
NCT04484532
Brief Title
Evaluation of Antibody Response to High-Dose Seasonal Influenza Vaccination in Patients With Myeloid Malignancy Receiving Chemotherapy and Healthy Volunteers
Official Title
Evaluation of Antibody Response to High-Dose Seasonal Influenza Vaccination in Patients With Myeloid Malignancy Receiving Chemotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
October 17, 2017 (Actual)
Primary Completion Date
June 7, 2022 (Actual)
Study Completion Date
June 7, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Roswell Park Cancer Institute
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
This pilot research trial studies the antibody response to high-dose seasonal influenza vaccination in patients with myeloid malignancy receiving chemotherapy and healthy volunteers. Evaluating antibody response to high-dose seasonal influenza vaccine may serve as a basis for vaccine recommendations in patients with myeloid malignancies and provide insights into the status of the immune system in these patients.
Detailed Description
PRIMARY OBJECTIVES:
I. To investigate the antibody response to influenza vaccination in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) receiving hypomethylating agents (decitabine or azacytidine) compared to normal healthy controls and those patients with similar disorders receiving cytarabine containing intensive chemotherapy or best supportive care.
II. To collect and store blood samples at different time points (prior to and after vaccination) for assessment of influenza specific T-cell subsets using tetramers by flow cytometry.
OUTLINE:
Within 14 days of baseline influenza titer, patients receive trivalent influenza vaccine intramuscularly (IM) on day 0 (patients in cohorts 1 and 5 receive the vaccine at any time, patients in cohorts 2 and 3 receive the vaccine between days 14-25 of hypomethylating agent therapy course, and patients in cohort 4 receive the vaccine between days 21-365 from onset of cytotoxic chemotherapy). Patients then undergo titer assessment at days 25-90 and days 115-185.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Myelodysplastic Syndrome
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
130 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Supportive Care (trivalent influenza vaccine)
Arm Type
Experimental
Arm Description
Within 14 days of baseline influenza titer, patients receive trivalent influenza vaccine IM on day 0 (patients in cohorts 1 and 5 receive the vaccine at any time, patients in cohorts 2 and 3 receive the vaccine between days 14-25 of hypomethylating agent therapy course, and patients in cohort 4 receive the vaccine between days 21-365 from onset of cytotoxic chemotherapy). Patients then undergo titer assessment at days 25-90 and days 115-185.
Intervention Type
Biological
Intervention Name(s)
Trivalent Influenza Vaccine
Other Intervention Name(s)
Agriflu, Flu prevention, Flu prophylaxis, Flu shot, Flu vaccination, Fluarix, Flublok, FluLaval, Flushield, Fluvirin, Fluzone High-dose (HD), Influenza Vaccine, Influenza Virus Vaccine, Trivalent, Types A and B, Trivalent Influenza Vaccine (TIV)
Intervention Description
Given IM
Primary Outcome Measure Information:
Title
Antibody response (by microneutralization assay) to influenza vaccination
Description
The geometric mean (GMT) and standard deviation of antibody titers will be calculated by cohort at the baseline assessment and 1-3 months post vaccination time points. Antibody response is assessed using the outcome measures: seroprotection, seroconversion, and GMT. Seroprotection is defined as an hemagglutination inhibition (HAI) titer >= 1:40 of each individual influenza antigen. Seroconversion is defined as >= 4-fold increase in post-vaccination titer of each individual influenza antigen. The seroprotection and seroconversion rates will be reported by age strata, cohort, and time-point (1-3 months and 4-6 months post vaccination) using 95% confidence intervals obtained using Jeffrey's prior method. The GMT at each time-point will be compared using one-sided permutation T-tests about the log-transformed data. The GMT ratio (GMTR) between 1-3 months post vaccination and baseline will also be calculated and reported by cohort using a 95% confidence interval.
Time Frame
Up to 4-6 months post-vaccination
Secondary Outcome Measure Information:
Title
T-cell subset population assessed using flow cytometry
Description
T-cell subset populations will be correlated with antibody responses to influenza vaccination. Blood samples will be collected and stored at different time-points for assessment of T-cell response to influenza vaccination using influenza specific tetramer staining by flow cytometry. The seroprotection and seroconversion rates will be reported by cohort and time-point (1-3 months and 4-6 months post vaccination) using 95% confidence intervals obtained using Jeffrey's prior method. The rates will be compared between the lenalidomide and healthy control cohorts using one-sided Barnard's tests. The GMTR between 1-3 months post vaccination and baseline will also be calculated and reported by cohort using a 95% confidence interval.
Time Frame
Up to 4-6 months post-vaccination
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Subject or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to undergoing any investigational biospecimen (blood) collection procedure
Willing to undergo seasonal influenza vaccination with Fluzone high dose at Roswell Park Cancer Institute within 2 weeks of enrollment of this study
Estimated survival of 8 weeks or more following enrollment on the study
Exclusion Criteria:
Uncontrolled intercurrent illness including, but not limited to, ongoing or active influenza infection or influenza-like-illness
Women who are attempting pregnancy or known to be pregnant by clinical history or nursing female subjects
Unwilling or unable to follow protocol requirements
Use of prednisone > 10 mg/day (or its equivalent for other steroids) for > 2 weeks immediately prior to receiving seasonal influenza vaccination
Received dose of seasonal influenza vaccination prior to enrollment
Participation at the time of study enrollment in another clinical trial investigating immunotherapeutic agents (like anti-PD1 or anti-PDL1 or anti-CTLA4 antibodies or vaccines); concurrent participation in an observational/non-interventional study or an interventional study investigating tyrosine kinase inhibitor or other targeted agents use is acceptable
Inability to receive seasonal influenza vaccine due to prior hypersensitivity to eggs, chicken proteins, or any of the vaccine components
History of a life-threatening reaction to influenza vaccination or to a vaccine containing similar substances
Personal history of Guillain-Barre syndrome
Any condition which in the investigator's opinion deems the subject an unsuitable candidate to receive annual influenza vaccination or may potentially affect the response to influenza vaccination
Adults unable to consent, individuals who are not yet adults (infants, children, and teenagers), women who are known to be pregnant, attempting pregnancy, or nursing women, and prisoners will be excluded from the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elizabeth A Griffiths
Organizational Affiliation
Roswell Park Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Evaluation of Antibody Response to High-Dose Seasonal Influenza Vaccination in Patients With Myeloid Malignancy Receiving Chemotherapy and Healthy Volunteers
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