Clinical trial NCT02447718: Vaccinating Children After Chemotherapy
Official title: Vaccinating Children After Chemotherapy for Acute Lymphoblastic Leukemia: A Canadian Immunization Research Network Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Lymphoblastic Leukemia
Lead sponsor: Canadian Immunization Research Network
Sponsor class: NETWORK
First posted: 2015-05-19
Enrollment: 156
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Percentage of Participants With Protective Titres to PCV13 Serotypes Post-immunization With PCV13+PPV23
timeFrame: Pre-vaccination Baseline, 2 months and 12-15 months
Secondary outcomes:
measure: Number of Participants With Protective Titres to PCV7 Serotypes at Baseline
timeFrame: Day 0
measure: Baseline Pneumococcal Antibody Titres in Subjects With ALL Versus Controls
timeFrame: Day 0
measure: Immune Responses to Pertussis Toxin Following DTaP-IPV-Hib Booster Vaccination
timeFrame: Prevaccination baseline, 2 months, 12-15 months
measure: Baseline Tetanus Toxoid Antibody Titers in Children With ALL Versus Controls
timeFrame: Day 0
measure: Baseline Pertussis Toxin Titers in Children With ALL Versus Healthy Controls
timeFrame: Day 0
measure: Baseline Varicella Titers in Children With ALL Versus Controls.
timeFrame: Day 0
measure: Immune Responses to Tetanus Toxoid Following DTaP-IPV-Hib Immunization
timeFrame: baseline, 2 months, 12-15 months
Other outcomes:
measure: Number of Participants With Adverse Events Following Immunization Requiring Healthcare Visit or Leading to >=1 Day of Disability
timeFrame: days 8-10 and 30-33
Locations:
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
Study officials:
affiliation: Dalhousie University
name: Karina Top, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
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.