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Vaccinating Children After Chemotherapy

Primary Purpose

Acute Lymphoblastic Leukemia

Status
Completed
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Prevnar®13
Pneumovax® 23
Pediacel®
Sponsored by
Canadian Immunization Research Network
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Acute Lymphoblastic Leukemia

Eligibility Criteria

3 Years - 18 Years (Child, Adult)All SexesAccepts Healthy Volunteers

Cases with ALL:

Inclusion Criteria:

  • Diagnosed with standard, high-risk or very-high risk ALL
  • Age at diagnosis: ≥1 year of age (age at enrollment: ≥3 years)
  • Completed chemotherapy 3 to 12 months prior to enrollment
  • No evidence of ALL relapse or secondary malignancy
  • No known primary immunodeficiency
  • No receipt of pneumococcal or tetanus-containing vaccines since completing chemotherapy
  • No history of allergy to any component of PCV13
  • Caregiver and/or participant is English or French-speaking and able to provide written informed consent

Exclusion Criteria:

  • Infantile ALL
  • Evidence of disease relapse or secondary malignancy
  • History of underlying primary immunodeficiency
  • Transplant recipient
  • Received intravenous immunoglobulin (IVIG) within past 9 months or other blood products within the prior 3 months.Children who received PPV23 within 12 months of enrollment will not be eligible to receive PCV13 or PPV23. These children can still participate in the baseline evaluation, receive DTaP-Hib-IPV vaccine, and have tetanus and pertussis serology measured at 2 and 12-15 months post-immunization.

Controls:

Inclusion criteria

  • Children 3-18 years of age, age-matched to cases
  • Caregiver and/or participant is English or French-speaking and able to provide written informed consent

Exclusion criteria

  • History of primary or secondary immunodeficiency including aplastic anemia, malignancy, nephrotic syndrome, malabsorption or severe malnutrition
  • Immunosuppressive therapy within 3 months of enrollment (excluding inhaled corticosteroids)
  • Received intravenous immunoglobulin (IVIG) within past 9 months or other blood products within the prior 3 months.

Sites / Locations

  • IWK Health Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

Experimental

Healthy Control

Arm Description

Children who were diagnosed with ALL at ≥1 year of age, and are within 6-8 months of completing chemotherapy will receive 1 dose each of: Prevnar®13 and Pediacel® vaccines, followed by 1 dose of Pneumovax® 23 given 2 months after PCV13.

Children 3-18 years of age who are not immunocompromised age-matched to cases from Group 1.

Outcomes

Primary Outcome Measures

Percentage of Participants With Protective Titres to PCV13 Serotypes Post-immunization With PCV13+PPV23
The percentage of participants with protective titres (with protective level defined as ≥0.35 ug/ml, as per World Health Organization criteria) to PCV13 serotypes will be assessed at 2 months and 12-15 months post PCV13+PPV23 and compared to baseline levels.

Secondary Outcome Measures

Number of Participants With Protective Titres to PCV7 Serotypes at Baseline
The number of participants with protective titres (≥0.35 ug/ml) to PCV7 serotypes at baseline will be compared to age-matched controls.
Baseline Pneumococcal Antibody Titres in Subjects With ALL Versus Controls
Baseline geometric mean titers (GMT) and percentage of subjects with protective titres to pneumococcal serotypes in children with ALL versus age-matched controls.
Immune Responses to Pertussis Toxin Following DTaP-IPV-Hib Booster Vaccination
Baseline, Short-term (baseline - 2 months after vaccination) and long-term (baseline - 12-15 months) vaccine responses to DTaP-IPV-Hib will be measured using GMT ratios.
Baseline Tetanus Toxoid Antibody Titers in Children With ALL Versus Controls
Baseline geometric mean titers (95% confidence intervals) reported as IU/ml in children with ALL versus controls
Baseline Pertussis Toxin Titers in Children With ALL Versus Healthy Controls
Baseline geometric mean titers (95% confidence intervals) reported as IU/ml in children with ALL versus controls
Baseline Varicella Titers in Children With ALL Versus Controls.
Geometric mean titers (95% confidence interval) in AI (antibody index)
Immune Responses to Tetanus Toxoid Following DTaP-IPV-Hib Immunization
Baseline, short-term (baseline to 2 months after vaccination) and long-term (baseline to 12-15 months) vaccine responses to DTaP-IPV-Hib will be measured using GMTs with 95% confidence intervals

Full Information

First Posted
May 13, 2015
Last Updated
June 22, 2022
Sponsor
Canadian Immunization Research Network
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1. Study Identification

Unique Protocol Identification Number
NCT02447718
Brief Title
Vaccinating Children After Chemotherapy
Official Title
Vaccinating Children After Chemotherapy for Acute Lymphoblastic Leukemia: A Canadian Immunization Research Network Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
November 16, 2015 (Actual)
Primary Completion Date
March 5, 2018 (Actual)
Study Completion Date
March 5, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Canadian Immunization Research Network

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This multi-center open label clinical trial aims to identify predictors of low antibody titers to vaccine antigens in children with ALL who completed chemotherapy in the prior 6 months, and to determine the immunogenicity and safety of diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis-Haemophilus influenzae type b (DTaP-IPV-Hib) and 13-valent pneumococcal conjugate vaccine (PCV13) booster immunization administered 6 months post-chemotherapy, followed by 23-valent pneumococcal polysaccharide vaccination (PPV23) 2 months later. The results will support the development of clinical practice guidelines for this population.
Detailed Description
Rationale and Aims: Children with acute lymphoblastic leukemia (ALL) have evidence of persistent immunosuppression following chemotherapy and may experience waning of immunity to vaccines received prior to treatment. There is no standard of care in Canada regarding immunologic evaluation or booster immunization of children with ALL after chemotherapy. This study aims to identify predictors of low baseline immunity to vaccine antigens in children with ALL and to evaluate the immunogenicity and safety of a standard immunization regimen: DTaP-IPV-Hib and PCV13 booster immunization administered 6 months post-chemotherapy, followed by PPV23. Study Design: This will be a multi-center open-label clinical trial in which children who were diagnosed with ALL at ≥1 year of age, and have not received immunizations other than influenza since completing chemotherapy will undergo immunologic evaluation and serologic testing for pneumococcus, tetanus, pertussis and varicella. They will then be immunized with PCV13, DTaP-IPV-Hib, regardless of immunization history [unless PPV23 was received within the prior 12 months]. Other routine vaccines required as per provincial and centre-specific immunization policies will also be administered. PPV23 will be administered 8 weeks after PCV13. Repeat serologic testing will be conducted at 2 months and 12-15 months after DTaP-IPV-Hib and PCV13 immunization to assess short and long-term immune responses. Adverse events following immunization (AEFI) will be captured through standardized telephone interviews on days 8-10 and 30-33 post-immunization that will capture local and systemic AEFI.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
156 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Experimental
Arm Type
Active Comparator
Arm Description
Children who were diagnosed with ALL at ≥1 year of age, and are within 6-8 months of completing chemotherapy will receive 1 dose each of: Prevnar®13 and Pediacel® vaccines, followed by 1 dose of Pneumovax® 23 given 2 months after PCV13.
Arm Title
Healthy Control
Arm Type
No Intervention
Arm Description
Children 3-18 years of age who are not immunocompromised age-matched to cases from Group 1.
Intervention Type
Biological
Intervention Name(s)
Prevnar®13
Other Intervention Name(s)
13- valent conjugate pneumococcal vaccine, PCV13
Intervention Description
A single dose of Prevnar®13 will be administered to subjects with ALL who are 6-12 months post-completion of chemotherapy.
Intervention Type
Biological
Intervention Name(s)
Pneumovax® 23
Other Intervention Name(s)
23-valent polysaccharide pneumococcal vaccine, PPV23
Intervention Description
A single dose of Pneumovax® 23 will be administered to subjects approximately 2 months after Prevnar®13
Intervention Type
Biological
Intervention Name(s)
Pediacel®
Other Intervention Name(s)
DTaP-IPV-Hib
Intervention Description
A single dose of Pediacel® will be administered to subjects with ALL who are 6-12 months post-completion of chemotherapy.
Primary Outcome Measure Information:
Title
Percentage of Participants With Protective Titres to PCV13 Serotypes Post-immunization With PCV13+PPV23
Description
The percentage of participants with protective titres (with protective level defined as ≥0.35 ug/ml, as per World Health Organization criteria) to PCV13 serotypes will be assessed at 2 months and 12-15 months post PCV13+PPV23 and compared to baseline levels.
Time Frame
Pre-vaccination Baseline, 2 months and 12-15 months
Secondary Outcome Measure Information:
Title
Number of Participants With Protective Titres to PCV7 Serotypes at Baseline
Description
The number of participants with protective titres (≥0.35 ug/ml) to PCV7 serotypes at baseline will be compared to age-matched controls.
Time Frame
Day 0
Title
Baseline Pneumococcal Antibody Titres in Subjects With ALL Versus Controls
Description
Baseline geometric mean titers (GMT) and percentage of subjects with protective titres to pneumococcal serotypes in children with ALL versus age-matched controls.
Time Frame
Day 0
Title
Immune Responses to Pertussis Toxin Following DTaP-IPV-Hib Booster Vaccination
Description
Baseline, Short-term (baseline - 2 months after vaccination) and long-term (baseline - 12-15 months) vaccine responses to DTaP-IPV-Hib will be measured using GMT ratios.
Time Frame
Prevaccination baseline, 2 months, 12-15 months
Title
Baseline Tetanus Toxoid Antibody Titers in Children With ALL Versus Controls
Description
Baseline geometric mean titers (95% confidence intervals) reported as IU/ml in children with ALL versus controls
Time Frame
Day 0
Title
Baseline Pertussis Toxin Titers in Children With ALL Versus Healthy Controls
Description
Baseline geometric mean titers (95% confidence intervals) reported as IU/ml in children with ALL versus controls
Time Frame
Day 0
Title
Baseline Varicella Titers in Children With ALL Versus Controls.
Description
Geometric mean titers (95% confidence interval) in AI (antibody index)
Time Frame
Day 0
Title
Immune Responses to Tetanus Toxoid Following DTaP-IPV-Hib Immunization
Description
Baseline, short-term (baseline to 2 months after vaccination) and long-term (baseline to 12-15 months) vaccine responses to DTaP-IPV-Hib will be measured using GMTs with 95% confidence intervals
Time Frame
baseline, 2 months, 12-15 months
Other Pre-specified Outcome Measures:
Title
Number of Participants With Adverse Events Following Immunization Requiring Healthcare Visit or Leading to >=1 Day of Disability
Description
Adverse Events Following Immunization requiring healthcare visit or leading to >=1 day of disability will be captured through structured telephone interviews on days 8-10 and 30-33 after each immunization
Time Frame
days 8-10 and 30-33

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Cases with ALL: Inclusion Criteria: Diagnosed with standard, high-risk or very-high risk ALL Age at diagnosis: ≥1 year of age (age at enrollment: ≥3 years) Completed chemotherapy 3 to 12 months prior to enrollment No evidence of ALL relapse or secondary malignancy No known primary immunodeficiency No receipt of pneumococcal or tetanus-containing vaccines since completing chemotherapy No history of allergy to any component of PCV13 Caregiver and/or participant is English or French-speaking and able to provide written informed consent Exclusion Criteria: Infantile ALL Evidence of disease relapse or secondary malignancy History of underlying primary immunodeficiency Transplant recipient Received intravenous immunoglobulin (IVIG) within past 9 months or other blood products within the prior 3 months.Children who received PPV23 within 12 months of enrollment will not be eligible to receive PCV13 or PPV23. These children can still participate in the baseline evaluation, receive DTaP-Hib-IPV vaccine, and have tetanus and pertussis serology measured at 2 and 12-15 months post-immunization. Controls: Inclusion criteria Children 3-18 years of age, age-matched to cases Caregiver and/or participant is English or French-speaking and able to provide written informed consent Exclusion criteria History of primary or secondary immunodeficiency including aplastic anemia, malignancy, nephrotic syndrome, malabsorption or severe malnutrition Immunosuppressive therapy within 3 months of enrollment (excluding inhaled corticosteroids) Received intravenous immunoglobulin (IVIG) within past 9 months or other blood products within the prior 3 months.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karina Top, MD, MS
Organizational Affiliation
Dalhousie University
Official's Role
Principal Investigator
Facility Information:
Facility Name
IWK Health Centre
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3K 6R8
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
32067048
Citation
Top KA, Vaudry W, Morris SK, Pham-Huy A, Pernica JM, Tapiero B, Gantt S, Price VE, Rassekh SR, Sung L, McConnell A, Rubin E, Chawla R, Halperin SA. Waning Vaccine Immunity and Vaccination Responses in Children Treated for Acute Lymphoblastic Leukemia: A Canadian Immunization Research Network Study. Clin Infect Dis. 2020 Dec 3;71(9):e439-e448. doi: 10.1093/cid/ciaa163.
Results Reference
derived

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Vaccinating Children After Chemotherapy

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