Vaccinating Children After Chemotherapy

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02447718
• Other study ID #: SI02
• Status: Completed
• Phase: Phase 4
• Start date: November 16, 2015
• Est. completion date: March 5, 2018

Study information

• Verified date: June 2022
• Source: Canadian Immunization Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 156
• Est. completion date: March 5, 2018
• Est. primary completion date: March 5, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 3 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• Prevnar®13
A single dose of Prevnar®13 will be administered to subjects with ALL who are 6-12 months post-completion of chemotherapy.
• Pneumovax® 23
A single dose of Pneumovax® 23 will be administered to subjects approximately 2 months after Prevnar®13
• Pediacel®
A single dose of Pediacel® will be administered to subjects with ALL who are 6-12 months post-completion of chemotherapy.

Locations

Country	Name	City	State
Canada	IWK Health Centre	Halifax	Nova Scotia

Sponsors (1)

Lead Sponsor	Collaborator
Canadian Immunization Research Network

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Adverse Events Following Immunization Requiring Healthcare Visit or Leading to >=1 Day of Disability	Adverse Events Following Immunization requiring healthcare visit or leading to >=1 day of disability will be captured through structured telephone interviews on days 8-10 and 30-33 after each immunization	days 8-10 and 30-33
Primary	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	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.	Day 0
Secondary	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.	Day 0
Secondary	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.	Prevaccination baseline, 2 months, 12-15 months
Secondary	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	Day 0
Secondary	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	Day 0
Secondary	Baseline Varicella Titers in Children With ALL Versus Controls.	Geometric mean titers (95% confidence interval) in AI (antibody index)	Day 0
Secondary	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	baseline, 2 months, 12-15 months