High Dose Flu Vaccine in Treating Children Who Have Undergone Donor Stem Cell Transplant
Condition: Hematopoietic Cell Transplantation Recipient; Malignant Neoplasm; Influenza
MeSH terms: Neoplasms
Intervention: Trivalent Influenza Vaccine; Quadrivalent Influenza Vaccine; Laboratory Biomarker Analysis
Intervention description: High dose Trivalent Influenza Vaccine given intramuscular; Standard dose Quadrivalent Influenza Vaccine given intramuscular; Correlative studies
Intervention MeSH terms: Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 170.0
Sex: All
Minimum age: 3 Years
Maximum age: 17 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        1. 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.

          2. 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. Inclusion criteria

                    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.

               2. 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, 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.