Clinical trial NCT04969601: Anti-Covid-19 Vaccine in Children With Acute Leukemia and Their Siblings
Official title: Anti-Covid-19 Vaccine Protection in Immunocompromised Children (1 to 15 Years Old) With Acute Leukemia and Their Siblings (≥12 Years Old). Phase I-II Trial Evaluating Post-vaccine Safety and Humoral and Cellular Immunogenicity.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Leukemia
Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2021-07-20
Enrollment: 76
Sex: ALL
Minimum age (years): 1
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Dose finding, stratified on the age group (≥1-\<2 years, ≥2-\<5 years, ≥5-\<12 years)
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

* 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 :

  * A negative blood test at the inclusion visit
  * 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

Exclusion Criteria:

* 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
* Pregnant, breast-feeding or positive pregnancy test at inclusion visit.
* Participation in a vaccination trial
* Participation in other research without investigator's consent research within 4 weeks prior to the inclusion visit and for the duration of the trial

Translated with DeepL.com (free version)

Primary outcomes:
measure: Dose limiting toxicity (DLT)
timeFrame: within 7 days from first dose
measure: co-primary endpoint: anti-Spike Immunoglobulin G (IgG) titer >= 260 BAU/mL
timeFrame: at 1 month from second dose
Secondary outcomes:
measure: Anti-Spike IgG levels
timeFrame: between 21 and 28 days from first dose
measure: Anti-Spike IgG levels
timeFrame: at 6 months from first dose
measure: Anti-Spike IgG levels
timeFrame: at 12 months from the 1st dose
measure: Anti-nucleocapsid IgG levels
timeFrame: between 21 and 28 days from the first dose
measure: Anti-nucleocapsid IgG levels
timeFrame: 6 months from the first dose
measure: Anti-nucleocapsid IgG levels
timeFrame: 12 months from the first dose
measure: Neutralization ability of anti-Spike IgG (in case of anti-Spike IgG detection)
timeFrame: at 2 months from the first injection
measure: Neutralization ability of anti-Spike IgG (in case of anti-Spike IgG detection)
timeFrame: at 6 months from the first injection
measure: Neutralization ability of anti-Spike IgG (in case of anti-Spike IgG detection)
timeFrame: at 12 months from the first injection
measure: Anti-SARS-CoV-2 T cell specific response (Elispot)
timeFrame: at 2 months after the first injection
measure: Anti-SARS-CoV-2 T cell specific response (Elispot)
timeFrame: at 6 months after the first injection
measure: Anti-SARS-CoV-2 T cell specific response (Elispot)
timeFrame: at 12 months after the first injection
measure: Positivity of SARS-CoV-2 polymerase chain reaction (PCR) in nasopharynx
timeFrame: at 8 days
measure: Positivity of SARS-CoV-2 PCR in nasopharynx
timeFrame: at 15 days
measure: Positivity of SARS-CoV-2 PCR in nasopharynx
timeFrame: at 28 days from infection
measure: Rate of symptomatic SARS-CoV-2 infections
timeFrame: within 12 months after vaccination
measure: Genotype of the SARS-CoV-2 variant in case of infection
timeFrame: within 12 months after vaccination
measure: Time between chemotherapy planned date and effective date in case of infection
timeFrame: within 12 months after vaccination
measure: Covid19 World Health Organization (WHO) progression scale
timeFrame: within 12 months after vaccination
measure: Incidence of SARS-CoV-2 of the household (contact cases)
timeFrame: within 12 months after vaccination
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Armand Trousseau
city: Paris
country: France
facility: Hôpital Robert Debré
Study officials:
References: