Vaccinating Children After Chemotherapy

NCT ID: NCT02447718

Last Updated: 2022-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 156 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-16
• Study Completion Date: 2018-03-05

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.

Conditions

Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Experimental

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.

Group Type: ACTIVE_COMPARATOR

Prevnar®13

Intervention Type: BIOLOGICAL

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

Pneumovax® 23

Intervention Type: BIOLOGICAL

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

Pediacel®

Intervention Type: BIOLOGICAL

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

Healthy Control

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Prevnar®13

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

Pneumovax® 23

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

Intervention Type: BIOLOGICAL

Pediacel®

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

Intervention Type: BIOLOGICAL

Other Intervention Names

13- valent conjugate pneumococcal vaccine; PCV13; 23-valent polysaccharide pneumococcal vaccine; PPV23; DTaP-IPV-Hib

Eligibility Criteria

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

• 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

• 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:

• 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.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Canadian Immunization Research Network

NETWORK

Sponsor Role: lead

Responsible Party

Karina Top

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Karina Top, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Dalhousie University

Locations

IWK Health Centre

Halifax, Nova Scotia, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 32067048 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

SI02

Identifier Type: -

Identifier Source: org_study_id