High Dose Flu Vaccine in Treating Children Who Have Undergone Donor Stem Cell Transplant

NCT ID: NCT02860039

Last Updated: 2024-10-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 170 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2024-09-30

Brief Summary

This phase II randomized trial studies how well high dose flu vaccine works in treating children who have undergone done stem cell transplant. Higher dose flu vaccine may build a better immune response and may provide better protection against the flu than the standard vaccine.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine whether high-dose trivalent inactivated influenza vaccine (HD-TIV) compared with standard dose quadrivalent inactivated influenza vaccine (QIV) will increase the probability of achieving a >= 4-fold rise in hemagglutination-inhibition (HAI) titers, >= 1:40 HAI titer, or higher geometric mean titer (GMT) to influenza A antigens in pediatric hematopoietic stem cell transplant (HSCT) recipients.

SECONDARY OBJECTIVES:

I. To determine whether HD-TIV compared with standard dose QIV will increase the probability of achieving a >= 4-fold rise in HAI titers, >= 1:40 HAI titer, or higher GMT titers to influenza B antigens in pediatric HSCT recipients.

II. To determine the frequency and severity of solicited local injection site adverse events (e.g. pain/ tenderness, redness, and swelling at injection site) with HD-TIV compared to standard QIV in pediatric HSCT recipients.

III. To determine the frequency and severity of solicited systemic adverse events (e.g. fevers, headache, fatigue/malaise, nausea, body ache/myalgia, general activity level, and vomiting) with HD-TIV compared to standard dose QIV in pediatric HSCT recipients.

IV. To define the relationship between HAI titers, in vivo T and B cell phenotype, and in vitro influenza-specific T and B cell response in pediatric HSCT recipients receiving either HD-TIV or standard dose QIV.

V. To correlate HAI responses to microneutralization responses.

VI. To compare the persistent HAI and microneutralization (MN) titers for all four antigen seven months after the last vaccine dose to assess for persistence of antibody titers.

VII. To compare influenza detection by PCR during influenza season in pediatric HSCT recipients receiving either HD-TIV or standard dose QIV.

VIII. To assess HAI and MN response in children vaccinated during year 1 and revaccinated during year 2 using the same antigen dose.

OUTLINE: Patients are randomized to 1 of 2 treatment groups.

GROUP I (Experimental): Patients receive HD-TIV intramuscularly (IM) on day 0 and day 28.

GROUP II (Standard): Patients receive standard dose QIV IM on day 0 and day 28.

After completion of study treatment, patients are followed up at 28-42 days, and at 7 months.

Conditions

Hematopoietic Cell Transplantation Recipient; Malignant Neoplasm; Influenza

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Group 1 - High Dose TIV

Patients receive HD-TIV intramuscularly (IM) on day 0 and day 28.

Group Type: EXPERIMENTAL

Trivalent Influenza Vaccine

Intervention Type: BIOLOGICAL

High dose Trivalent Influenza Vaccine given intramuscular

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Group 2 - Standard Dose QIV

Patients receive standard dose QIV IM on day 0 and day 28.

Group Type: ACTIVE_COMPARATOR

Quadrivalent Influenza Vaccine

Intervention Type: BIOLOGICAL

Standard dose Quadrivalent Influenza Vaccine given intramuscular

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Interventions

Trivalent Influenza Vaccine

High dose Trivalent Influenza Vaccine given intramuscular

Intervention Type: BIOLOGICAL

Quadrivalent Influenza Vaccine

Standard dose Quadrivalent Influenza Vaccine given intramuscular

Intervention Type: BIOLOGICAL

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Allogeneic HSCT recipients who are 3-35 months post-transplant;

2. 3-17 years of age, inclusive;

3. Available for duration of study;

4. Patients with stable GVHD for at least 4 weeks will be eligible (stable is defined as having no major increases in systemic immunosuppressive therapy for GVHD; adjustments of established medications to obtain a stable target level are acceptable and do not impact eligibility). Parent/legal guardian willing and capable of signing written informed consent;

5. Parent/legal guardian expected to be available for entire study;

6. Parent/legal guardian can be reached by telephone and/or electronic communication.

7. Subjects must have a platelet count of ≥30,000 to receive the immunizations. Patients requiring platelet transfusions are eligible to enroll and must have a platelet count ≥30,000 within 72 hours prior to their immunization, or platelet count ≥75,000 without transfusion documented within 30 days for subjects <12 months post-transplant and within 90 days for subjects 12-35 months post-transplant.

1. Available for duration of study;

2. Patients with stable GVHD for at least 4 weeks will be eligible (stable is defined as no major change in systemic immunosuppressive therapy for worsening GVHD; adjustment of actual dose to obtain a stable target level is acceptable).

3. Subjects must have a platelet count of ≥30,000 to receive the immunizations. Patients requiring platelet transfusions are eligible to enroll and must have a platelet count ≥30,000 within 72 hours prior to their immunization, or platelet count ≥75,000 without transfusion documented within 30 days for subjects <12 months post-transplant and within 90 days for subjects 12-35 months post-transplant.

4. Parent/legal guardian willing and capable of signing written informed consent;

5. Parent/legal guardian expected to be available for entire study;

6. Parent/legal guardian can be reached by telephone and/or electronic communication.

Exclusion Criteria

1. History of hypersensitivity to previous influenza vaccination or severe hypersensitivity to eggs/egg protein;

2. History of Guillain-Barre syndrome;

3. Evidence of hematologic malignancy or disease relapse post-transplant (stable mixed chimerism is permitted);

4. History of receiving current year seasonal influenza vaccine post-transplant;

5. Pregnant female;

6. History of proven influenza disease after September 1, 2018 prior to enrollment

7. Non-allogeneic (e.g. autologous) or syngeneic hematopoietic SCT recipients;

8. History of known active infection with HIV, Hepatitis B or Hepatitis C;

9. History of known severe latex hypersensitivity;

10. Subjects who have received stem cell boost or delayed donor lymphocyte infusion within 90 days prior to enrollment, including day of enrollment;

11. Receipt of IVIG/SCIG <27 days prior to calendar day of vaccination;

12. Subjects who have participated in year 1 and/or 2 of the study, and received study vaccine

Criteria for temporarily delaying vaccine administration: The following conditions are temporary or self-limiting, and a subject may be included in the study once the condition has resolved, provided that the subject is otherwise eligible: 1). Fever ≥100.4ºF/38.0ºC (oral measurement), or an acute illness within 48 hours of enrollment 2). Receipt of any live vaccines within four weeks or any inactivated vaccines within two weeks prior to potential study vaccination.

Note: if patients were eligible for vaccine 1, they will be eligible to receive vaccine 2 regardless of any changes on their GVHD status, unless it is deemed not medically safe to receive influenza vaccine.

For subjects who were enrolled and vaccinated in 2016-17, 2017-18, or 2018-19, the goal is to enroll individuals who participated in the previous influenza season year and administer the same vaccination as the previous year. These subjects are referred to as repeaters. For example, subjects enrolled in 2016-17 could re-enroll in 2017-18, subjects enrolled in 2017-18 could re-enroll in 2018-19, and subjects in 2018-19 are deemed eligible to re-enroll in 2019-20 as repeaters. Subjects may only enroll as a repeater one time and must enroll the year after their original enrollment. Subjects must receive at least one vaccine to be eligible as a repeater in the subsequent year.

Enrollment Criteria for Subjects who Participated in the previous influenza season

• Repeaters will retain their original study ID and their randomization number
• Previous screen failures will not be enrolled.
• If visit 4 from the previous influenza season and visit 1 from the current influenza season year occur on the same day, lab results from visit 4 (prior to consent) can be part of visit 1.

1. History of hypersensitivity to previous influenza vaccination or severe hypersensitivity to eggs/egg protein;

2. History of Guillain-Barre syndrome;

3. Evidence of hematologic malignancy or disease relapse post-transplant (stable mixed chimerism is permitted);

4. History of receiving current year seasonal influenza vaccine post-transplant;

5. Pregnant female;

6. History of proven influenza disease after September 1, 2019 but prior to enrollment

7. History of known active infection with HIV, Hepatitis B or Hepatitis C;

8. Subjects who have received stem cell boost or delayed donor lymphocyte infusion within 90 days of enrollment, including day of enrollment

9. Receipt of IVIG/SCIG <27 days prior to calendar day of vaccination

10. Non-allogeneic (e.g. autologous) or syngeneic hematopoietic SCT recipients;

11. Subjects who have participated in year 1 and/or 2 of the study and received study vaccine.

Criteria for temporarily delaying vaccine administration: The following conditions are temporary or self-limiting, and a subject may be included in the study once the condition has resolved, provided that the subject is otherwise eligible: 1). Fever ≥100.4ºF/38.0ºC (oral measurement), or an acute illness within 48 hours of enrollment 2). Receipt of any live vaccines within four weeks or any inactivated vaccines within two weeks prior to potential study vaccination.

Note: if patients were eligible for vaccine 1, they will be eligible to receive vaccine 2 regardless of any changes on their GVHD status, unless it is deemed not medically safe to receive influenza vaccine.

Note: Previous Screen failures who were not vaccinated can be enrolled and will be assigned the same study ID number.

Criteria for temporarily delaying vaccine administration: The following conditions are temporary or self-limiting, and a subject may be included in the study once the condition has resolved, provided that the subject is otherwise eligible: 1). Fever ≥100.4ºF/38.0ºC (oral measurement), or an acute illness within 48 hours of enrollment 2). Receipt of any live vaccines within four weeks or any inactivated vaccines within two weeks of study vaccination.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Vanderbilt-Ingram Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Natasha Halasa, MD

Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Natasha Halasa, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University

Locations

UCSF Children's Hospital

San Francisco, California, United States

Children's Mercy Hospital

Kansas City, Missouri, United States

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Texas Children's Hospital

Houston, Texas, United States

Seattle Children's Hospital Research Institute

Seattle, Washington, United States

Countries

United States

References

Bahakel H, Spieker AJ, Hayek H, Schuster JE, Hamdan L, Dulek DE, Kitko CL, Stopczynski T, Batarseh E, Haddadin Z, Stewart LS, Stahl A, Potter M, Rahman H, Amarin J, Kalams SA, Bocchini CE, Moulton EA, Coffin SE, Ardura MI, Wattier RL, Maron G, Grimley M, Paulsen G, Harrison CJ, Freedman J, Carpenter PA, Englund JA, Munoz FM, Danziger-Isakov L, Halasa N; Pediatric HCT Flu Study. Immunogenicity and Reactogenicity of High- or Standard-Dose Influenza Vaccine in a Second Consecutive Influenza Season. J Infect Dis. 2025 Feb 4;231(1):e123-e131. doi: 10.1093/infdis/jiae454.

Reference Type: DERIVED

PMID: 39279435 (View on PubMed)

Schuster JE, Hamdan L, Dulek DE, Kitko CL, Batarseh E, Haddadin Z, Stewart LS, Stahl A, Potter M, Rahman H, Kalams SA, Bocchini CE, Moulton EA, Coffin SE, Ardura MI, Wattier RL, Maron G, Grimley M, Paulsen G, Harrison CJ, Freedman JL, Carpenter PA, Englund JA, Munoz FM, Danziger-Isakov L, Spieker AJ, Halasa NB; Pediatric HCT Flu Study. The Durability of Antibody Responses of Two Doses of High-Dose Relative to Two Doses of Standard-Dose Inactivated Influenza Vaccine in Pediatric Hematopoietic Cell Transplant Recipients: A Multi-Center Randomized Controlled Trial. Clin Infect Dis. 2024 Jan 25;78(1):217-226. doi: 10.1093/cid/ciad534.

Reference Type: DERIVED

PMID: 37800415 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

NCI-2016-01090

Identifier Type: REGISTRY

Identifier Source: secondary_id

VICC PED 1647

Identifier Type: -

Identifier Source: org_study_id