Vaccinating Children After Chemotherapy

Canadian Immunization Research Network

Status and phase: Completed; Phase 4

Conditions: Acute Lymphoblastic Leukemia

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

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT02447718

SI02

Details and patient eligibility

About

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.

Full 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.

Enrollment: 156 patients

Sex: All

Ages: 3 to 18 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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156 participants in 2 patient groups

Experimental

Active Comparator group

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.

Treatment:

Biological: Prevnar®13

Biological: Pediacel®

Biological: Pneumovax® 23

Healthy Control

No Intervention group

Description:

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