Anti-Covid-19 Vaccine in Children With Acute Leukemia and Their Siblings

NCT04969601 | Completed Phase 1 DMC

• 1 other identifier: APHP210639
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 2

Brief Summary

Mortality in case of SARS-CoV-2 infection (Covid-19) during acute leukemia (AL) treatment is around 30%, i.e. more than 10 times the one of general population. Severe forms are reported in children receiving chemotherapy for AL. However, the main risk, largely underestimated, is related to delay in chemotherapy administration in case of infection, leading to an increased risk of relapse. Therefore, it is justified to propose an anti-Covid-19 vaccination to these patients. Vaccination of siblings also seems necessary given the uncertainty regarding vaccine response in children with AL and given that household is the main source of contamination. The messenger ribonucleic acid (mRNA) vaccine COMIRNATY® (BNT162b2) is already approved by health authorities for individuals older than 12. In immunocompromised children with AL, safety and efficacy data are unknown. The benefit/risk balance encourages to use the vaccine without health authority approval in children aged 1 to 15 with AL. Regarding household, parents are vaccinated for several months as standard of care, but vaccination will be proposed to siblings aged 5 to 15 years old in this protocol. The primary objective of this study is to evaluate safety and immunogenicity of COMIRNATY® (BNT162b2) vaccine (two injections 21-28 days apart) in children with acute leukemia (1 to 15 years old) and their siblings (5 to 15 years old). A secondary objective of the study is to compare the quality of humoral and cellular vaccine responses in children with AL and healthy children.

Conditions

Acute Leukemia; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity (DLT)

  Dose limiting toxicity (DLT) defined by the presence within 7 days following vaccine injection of a grade ≥3 adverse event related to the vaccine. They are derived from CTCAE v5.0 and FDA guide " Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials ". Any other unexpected grade 3-4 clinical adverse event according to CTCAE v5.0 related to vaccination. A committee of critical events and DLTs surveillance will validate if declared grade 3-4 serious adverse events are related to vaccine.

  within 7 days from first dose

• co-primary endpoint: anti-Spike Immunoglobulin G (IgG) titer >= 260 BAU/mL

  Quantitative detection of anti-spike antibodies by chemiluminescence technique

  at 1 month from second dose

Secondary Outcomes (20)

• Anti-Spike IgG levels

  between 21 and 28 days from first dose

• Anti-Spike IgG levels

  at 6 months from first dose

• Anti-Spike IgG levels

  at 12 months from the 1st dose

• Anti-nucleocapsid IgG levels

  between 21 and 28 days from the first dose

• Anti-nucleocapsid IgG levels

  6 months from the first dose

Study Arms (1)

Anti Covid with COMIRNATY® (BNT162b2) vaccine

EXPERIMENTAL

Two injections of COMIRNATY® (BNT162b2) vaccine 21-28 days apart

Biological: vaccine COMIRNATY® (BNT162b2)

Interventions

vaccine COMIRNATY® (BNT162b2) BIOLOGICAL

two injections of COMIRNATY® (BNT162b2) vaccine 21-28 days apart, of either 10, 20, 30 µg of vaccine, depending on the observed responses of previous children

Anti Covid with COMIRNATY® (BNT162b2) vaccine

Eligibility Criteria

• Age: 1 Year - 15 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Children aged 1 to 15 years old :
• With acute lymphoblastic leukemia undergoing chemotherapy (at least 2 weeks from the last injection of PEG-asparaginase) or for whom the last chemotherapy is less than or equal to 12 months
• OR With acute myeloid leukemia within 12 months from the end of treatment
• Healthy siblings aged 5 to 15 years old living in the same household than the child with AL more than 50% of the time
• Informed consent from parents
• Patient affiliated to health insurance
• For women of childbearing age :
• AND use of an effective contraceptive method at least at least 4 weeks prior to vaccination and until at least 12 weeks after the last vaccination

You may not qualify if:

• Documented SARS-CoV-2 infection ongoing or that occurred less than 2 months ago
• Known clinical allergy to polyethylene glycol (PEG)
• Platelet \<50 Giga(G) G/L or neutrophils \<0.5 G/L at time of vaccination
• Vaccination apart from influenza virus within 4 weeks from the 1st injection or planning to receive an approved vaccine 4 weeks after the last injection
• Vaccination against influenza virus within 14 days before first injection
• Any hemorrhagic trouble considered as a contraindication to intramuscular injection
• History of severe adverse event after a vaccine administration including anaphylaxis and associated symptoms such as rash, respiratory issues, angioedema and abdominal pain, or history of allergic reaction that could be exacerbated by a vaccine component
• Participant vaccinated against tuberculosis within the past year
• Participant ill or febrile (body temperature ≥38°C) in the previous 72 hours with symptoms suggesting the presence of COVID-19.
• Allergy to any component of the vaccine or history of severe allergy (anaphylactic type)
• Treatment received for Covid-19 infection (60 days prior to 1st injection).
• Known HIV, HCV or HBV infection.
• Use of experimental Ig, experimental monoclonal antibodies or convalescent anti-covid-19 serum within 90 days prior to study entry
• Participation in a vaccination trial
• Translated with DeepL.com (free version)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (2)

Hôpital Armand Trousseau

Paris, 75012, France

Location

Hôpital Robert Debré

Paris, 75019, France

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute

Interventions

BNT162 Vaccine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid

Intervention Hierarchy (Ancestors)

mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines; Antigens; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Dose finding, stratified on the age group (≥1-\<2 years, ≥2-\<5 years, ≥5-\<12 years)

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: July 20, 2021
• Study Start: September 29, 2021
• Primary Completion: February 28, 2022
• Study Completion: March 1, 2024
• Last Updated: June 26, 2024

Record last verified: 2024-06

Locations

FR (2)