Acute Lymphoblastic LeukemiaPhase 4NCT02447718

Vaccinating Children After Chemotherapy

A Phase 4 study testing Prevnar®13, Pneumovax® 23 and Pediacel® in people with Acute Lymphoblastic Leukemia, run by Canadian Immunization Research Network at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 3 to 18 yearsHealthy volunteers can take part
Conditions the study is for: Acute Lymphoblastic Leukemia
What is being tested?: Prevnar®13, Pneumovax® 23 and Pediacel®
Type of treatment: Vaccines
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 156 participants
Where: 1 siteCanada
Study dates: 16 Nov 2015to 5 Mar 2018
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 3 to 18 years
All sexes
Healthy volunteers accepted
Child, Adult

Who may be able to join

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

Show all 10Show fewer

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
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

Who cannot join

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:

Show all 9Show fewer

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.

Trial locations and contacts

1 site in 1 country.

Canada1 site

IWK Health Centre
Halifax, Nova Scotia, B3K 6R8

Other trials in Canada

About this study

Official title: Vaccinating Children After Chemotherapy for Acute Lymphoblastic Leukemia: A Canadian Immunization Research Network Study

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.

Read the 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.

Conditions: Acute Lymphoblastic Leukemia
Being tested: Prevnar®13, Pneumovax® 23, Pediacel®
Medical subject headings: Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Prevnar®13Biological
Also called 13- valent conjugate pneumococcal vaccine, PCV13
A single dose of Prevnar®13 will be administered to subjects with ALL who are 6-12 months post-completion of chemotherapy.
Pneumovax® 23Biological
Also called 23-valent polysaccharide pneumococcal vaccine, PPV23
A single dose of Pneumovax® 23 will be administered to subjects approximately 2 months after Prevnar®13
Pediacel®Biological
Also called DTaP-IPV-Hib
A single dose of Pediacel® will be administered to subjects with ALL who are 6-12 months post-completion of chemotherapy.

Study groups in NCT02447718
Study group	Role	What they receive
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. Receives: Biological: Prevnar®13; Biological: Pneumovax® 23; Biological: Pediacel®
Healthy Control	No intervention	Children 3-18 years of age who are not immunocompromised age-matched to cases from Group 1.

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Pre-vaccination Baseline, 2 months and 12-15 months

Secondary outcomes (7)

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.
Measured: Day 0
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.
Measured: Day 0
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.
Measured: Prevaccination baseline, 2 months, 12-15 months
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
Measured: Day 0
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
Measured: Day 0
Baseline Varicella Titers in Children With ALL Versus Controls.
Geometric mean titers (95% confidence interval) in AI (antibody index)
Measured: Day 0
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
Measured: baseline, 2 months, 12-15 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Nov 20155 Mar 2018

First posted19 May 2015 (estimated)
Study start16 Nov 2015
Primary completion5 Mar 2018
Study completion5 Mar 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Prevention
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 156 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02447718
Sponsor's protocol ID: SI02
Status last verified: Jun 2022
First submitted: 13 May 2015
Last updated: 24 Jun 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 32067048

Study at a glance

From the registry record, last updated by the sponsor on 24 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Vaccinating Children After Chemotherapy for Acute Lymphoblastic Leukemia: A Canadian Immunization Research Network Study
ClinicalTrials.gov ID: NCT02447718
Acronym / sponsor ID: SI02
Conditions: Acute Lymphoblastic Leukemia
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 156 participants (actual)
Lead sponsor: Canadian Immunization Research NetworkResearch network
Study start: 16 Nov 2015 (actual)
Primary completion: 5 Mar 2018 (actual)
Study completion: 5 Mar 2018 (actual)
First posted: 19 May 2015 (estimated)
Results: Posted 4 Feb 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Prevention
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Experimental	Active comparator	Biological: Prevnar®13, Biological: Pneumovax® 23, Biological: Pediacel®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.
Healthy Control	No intervention	–Children 3-18 years of age who are not immunocompromised age-matched to cases from Group 1.

Who may qualify

Ages: 3 to 18 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child, Adult

Key inclusion criteria (10 listed)

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

Key exclusion criteria (9 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Prevnar®13Also: 13- valent conjugate pneumococcal vaccine, PCV13A single dose of Prevnar®13 will be administered to subjects with ALL who are 6-12 months post-completion of chemotherapy.	Biological	Experimental
Pneumovax® 23Also: 23-valent polysaccharide pneumococcal vaccine, PPV23A single dose of Pneumovax® 23 will be administered to subjects approximately 2 months after Prevnar®13	Biological	Experimental
Pediacel®Also: DTaP-IPV-HibA single dose of Pediacel® will be administered to subjects with ALL who are 6-12 months post-completion of chemotherapy.	Biological	Experimental

Primary outcome

Percentage of Participants With Protective Titres to PCV13 Serotypes Post-immunization With PCV13+PPV23
Time frame: Pre-vaccination Baseline, 2 months and 12-15 months
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.

7 secondary outcomes

Number of Participants With Protective Titres to PCV7 Serotypes at Baseline
Time frame: Day 0
Baseline Pneumococcal Antibody Titres in Subjects With ALL Versus Controls
Time frame: Day 0
Immune Responses to Pertussis Toxin Following DTaP-IPV-Hib Booster Vaccination
Time frame: Prevaccination baseline, 2 months, 12-15 months
Baseline Tetanus Toxoid Antibody Titers in Children With ALL Versus Controls
Time frame: Day 0
Baseline Pertussis Toxin Titers in Children With ALL Versus Healthy Controls
Time frame: Day 0
Baseline Varicella Titers in Children With ALL Versus Controls.
Time frame: Day 0
Immune Responses to Tetanus Toxoid Following DTaP-IPV-Hib Immunization
Time frame: baseline, 2 months, 12-15 months

Results and safety

Results posted to the registry on 4 Feb 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Experimental	78	66
Healthy Control	78	78

Primary outcome: Percentage of Participants With Protective Titres to PCV13 Serotypes Post-immunization With PCV13+PPV23

Time frame: Pre-vaccination Baseline, 2 months and 12-15 months. Count of participants. Unit: Participants

Measure	Experimental n = 66
2 months post-PCV13	40
12-15 months post-PCV13	22

Population analysed: Participants analyzed equaled the overall number of ALL participants that completed the study and had analyzable serology collected at 2 months and 12-15 months post-vaccination.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: AEFI was captured through structured telephone interviews on days 8-10 and 30-33 after each immunization. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
DTaP-IPV-HiB+PCV13	0 of 74 (0%)	56 of 74 (75.7%)	0 of 74
PPV23	0 of 73 (0%)	46 of 73 (63%)	0 of 73

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32067048Top 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Karina Top, MD, MS principal investigator

Dalhousie University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Prevnar®13, Pneumovax® 23 and Pediacel® in people with Acute Lymphoblastic Leukemia, run by Canadian Immunization Research Network at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Protective Titres to PCV13 Serotypes Post-immunization With PCV13+PPV23 (time frame: Pre-vaccination Baseline, 2 months and 12-15 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02447718, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2022; AzTrials last refreshed its copy on 31 Oct 2026.