NCT02447718

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
156

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started Nov 2015

Typical duration for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 13, 2015

Completed
6 days until next milestone

First Posted

Study publicly available on registry

May 19, 2015

Completed
6 months until next milestone

Study Start

First participant enrolled

November 16, 2015

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 5, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 5, 2018

Completed
2.9 years until next milestone

Results Posted

Study results publicly available

February 4, 2021

Completed
Last Updated

June 24, 2022

Status Verified

June 1, 2022

Enrollment Period

2.3 years

First QC Date

May 13, 2015

Results QC Date

October 8, 2020

Last Update Submit

June 22, 2022

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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.

    Pre-vaccination Baseline, 2 months and 12-15 months

Secondary Outcomes (7)

  • Number of Participants With Protective Titres to PCV7 Serotypes at Baseline

    Day 0

  • Baseline Pneumococcal Antibody Titres in Subjects With ALL Versus Controls

    Day 0

  • Immune Responses to Pertussis Toxin Following DTaP-IPV-Hib Booster Vaccination

    Prevaccination baseline, 2 months, 12-15 months

  • Baseline Tetanus Toxoid Antibody Titers in Children With ALL Versus Controls

    Day 0

  • Baseline Pertussis Toxin Titers in Children With ALL Versus Healthy Controls

    Day 0

  • +2 more secondary outcomes

Other Outcomes (1)

  • Number of Participants With Adverse Events Following Immunization Requiring Healthcare Visit or Leading to >=1 Day of Disability

    days 8-10 and 30-33

Study Arms (2)

Experimental

ACTIVE COMPARATOR

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.

Biological: Prevnar®13Biological: Pneumovax® 23Biological: Pediacel®

Healthy Control

NO INTERVENTION

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

Interventions

Prevnar®13BIOLOGICAL

A single dose of Prevnar®13 will be administered to subjects with ALL who are 6-12 months post-completion of chemotherapy.

Also known as: 13- valent conjugate pneumococcal vaccine, PCV13
Experimental
Pneumovax® 23BIOLOGICAL

A single dose of Pneumovax® 23 will be administered to subjects approximately 2 months after Prevnar®13

Also known as: 23-valent polysaccharide pneumococcal vaccine, PPV23
Experimental
Pediacel®BIOLOGICAL

A single dose of Pediacel® will be administered to subjects with ALL who are 6-12 months post-completion of chemotherapy.

Also known as: DTaP-IPV-Hib
Experimental

Eligibility Criteria

Age3 Years - 18 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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:
  • 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
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

23-valent pneumococcal capsular polysaccharide vaccinediphtheria-tetanus-five component acellular pertussis-inactivated poliomyelitis -Haemophilus influenzae type b conjugate vaccine

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Limitations and Caveats

1. Antibody levels to vaccine antigens were not measured before chemotherapy, cannot confirm that chemotherapy was the cause of low postchemotherapy titers. 2. Immunization status at ALL diagnosis was not assessed and therefore could not confirm whether postchemotherapy participants were underimmunized for age before diagnosis relative to their peers. 3. We were unable to assess antibodies to other pertussis antigens (eg, filamentous hemagglutinin, pertactin), only anti-PT antibodies alone.

Results Point of Contact

Title
Dr. Karina Top
Organization
IWK Health Centre

Study Officials

  • Karina Top, MD, MS

    Dalhousie University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
NETWORK
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

May 13, 2015

First Posted

May 19, 2015

Study Start

November 16, 2015

Primary Completion

March 5, 2018

Study Completion

March 5, 2018

Last Updated

June 24, 2022

Results First Posted

February 4, 2021

Record last verified: 2022-06

Locations