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

NCT02860039 | Completed Phase 2 Results DMC

• 2 other identifiers: VICC PED 1647NCI-2016-01090
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 9

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.

Conditions

Hematopoietic Cell Transplantation Recipient; Malignant Neoplasm; Influenza

Outcome Measures

Primary Outcomes (1)

• Immunogenicity as Measured by the Number of Subjects Who Achieve a 4-fold (or Greater) Rise in Post-vaccination HAI Titers

  Point estimates and 95% confidence intervals for proportion of subjects achieving seroconversion (4-fold or greater rise in HAI titers from visit 1).

  Visit 1 (baseline) was day 0; visit 2 was 28-42 days after visit 1; visit 3 was 28-42 days after visit 2; and visit 4 was 138-222 days after visit 2.

Secondary Outcomes (4)

• Proportion of Solicited Local and Systemic Adverse Events

  Up to 7 days following each vaccination: up to day 7 for vaccine 1 and up to day 35-49 for vaccine 2

• T and B Cell Phenotype Assessed by Mass Cytometry

  Visit 1 (baseline) was day 0; visit 2 was 28-42 days after visit 1; visit 3 was 28-42 days after visit 2; and visit 4 was 138-222 days after visit 2.

• T and B Cell Response Assessed by Mass Cytometry and In-vitro Functionality Assays

  Visit 1 (baseline) was day 0; optional visit 1 was 5-10 days after visit 1; visit 2 was 28-42 days after visit 1; optional visit 2 was 5-10 days after visit 2; visit 3 was 28-42 days after visit 2; and visit 4 was 138-222 days after visit 2.

• Percentage of Individuals in Each Group Who Test Positive for Influenza

  During the influenza season, up to 6 months

Study Arms (2)

Group 1 - High Dose TIV

EXPERIMENTAL

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

Biological: Trivalent Influenza Vaccine; Other: Laboratory Biomarker Analysis

Group 2 - Standard Dose QIV

ACTIVE COMPARATOR

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

Biological: Quadrivalent Influenza Vaccine; Other: Laboratory Biomarker Analysis

Interventions

Trivalent Influenza Vaccine BIOLOGICAL

High dose Trivalent Influenza Vaccine given intramuscular

Group 1 - High Dose TIV

Quadrivalent Influenza Vaccine BIOLOGICAL

Standard dose Quadrivalent Influenza Vaccine given intramuscular

Group 2 - Standard Dose QIV

Laboratory Biomarker Analysis OTHER

Correlative studies

Group 1 - High Dose TIV; Group 2 - Standard Dose QIV

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Allogeneic HSCT recipients who are 3-35 months post-transplant;
• years of age, inclusive;
• Available for duration of study;
• 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;
• Parent/legal guardian expected to be available for entire study;
• Parent/legal guardian can be reached by telephone and/or electronic communication.
• 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.

You may not qualify if:

• History of hypersensitivity to previous influenza vaccination or severe hypersensitivity to eggs/egg protein;
• History of Guillain-Barre syndrome;
• Evidence of hematologic malignancy or disease relapse post-transplant (stable mixed chimerism is permitted);
• History of receiving current year seasonal influenza vaccine post-transplant;
• Pregnant female;
• History of proven influenza disease after September 1, 2018 prior to enrollment
• Non-allogeneic (e.g. autologous) or syngeneic hematopoietic SCT recipients;
• History of known active infection with HIV, Hepatitis B or Hepatitis C;
• History of known severe latex hypersensitivity;
• Subjects who have received stem cell boost or delayed donor lymphocyte infusion within 90 days prior to enrollment, including day of enrollment;
• Receipt of IVIG/SCIG \<27 days prior to calendar day of vaccination;
• 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.

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (9)

UCSF Children's Hospital

San Francisco, California, 94158, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital Research Institute

Seattle, Washington, 98101, United States

Location

Related Publications (2)

• 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.

  PMID: 39279435 DERIVED

• 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.

  PMID: 37800415 DERIVED

MeSH Terms

Conditions

Neoplasms; Influenza, Human

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Natasha Halasa, MD, MPH
• Organization: Vanderbilt-Ingram Cancer Center

natasha.halasa@vumc.org

800-811-8480

Study Officials

• Natasha Halasa, MD, MPH

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: August 4, 2016
• First Posted: August 9, 2016
• Study Start: September 1, 2016
• Primary Completion: December 1, 2021
• Study Completion: September 1, 2024
• Last Updated: October 22, 2024
• Results First Posted: April 14, 2022

Record last verified: 2024-10

Locations

US (9)