Acute Leukemia, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
Conditions
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.
Interventions
BIOLOGICALvaccine COMIRNATY® (BNT162b2)
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
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Dose finding, stratified on the age group (≥1-\<2 years, ≥2-\<5 years, ≥5-\<12 years)
Eligibility
Sex/Gender
ALL
Age
1 Years to 15 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose limiting toxicity (DLT) | within 7 days from first dose | 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. |
| co-primary endpoint: anti-Spike Immunoglobulin G (IgG) titer >= 260 BAU/mL | at 1 month from second dose | Quantitative detection of anti-spike antibodies by chemiluminescence technique |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neutralization ability of anti-Spike IgG (in case of anti-Spike IgG detection) | at 2 months from the first injection | — |
| Anti-SARS-CoV-2 T cell specific response (Elispot) | at 2 months after the first injection | — |
| Positivity of SARS-CoV-2 polymerase chain reaction (PCR) in nasopharynx | at 8 days | Positivity of SARS-CoV-2 PCR in nasopharynx in case of infection |
| Positivity of SARS-CoV-2 PCR in nasopharynx | at 15 days | Positivity of SARS-CoV-2 PCR in nasopharynx in case of infection |
| Anti-Spike IgG levels | between 21 and 28 days from first dose | — |
| Genotype of the SARS-CoV-2 variant in case of infection | within 12 months after vaccination | — |
| Time between chemotherapy planned date and effective date in case of infection | within 12 months after vaccination | — |
| Covid19 World Health Organization (WHO) progression scale | within 12 months after vaccination | Covid19 WHO scale in 10 items in case of infection Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by non-invasive ventilation (NIV) or High flow: 6 Intubation and Mechanical ventilation, pO2/Fraction of inspired oxygen (FIO2)\>=150 OR saturation by pulse oximetry (SpO2) SpO2/FIO2\>=200: 7 Mechanical ventilation, (pO2/FIO2\<150 OR SpO2/FIO2\<200) OR vasopressors (norepinephrine \>0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2\<150 AND vasopressors (norepinephrine \>0.3 microg/kg/min), OR Dialysis OR extracorporeal membrane oxygenation (ECMO): 9 Dead: 10 |
| Incidence of SARS-CoV-2 of the household (contact cases) | within 12 months after vaccination | In case of infection in a vaccinated child |
| Rate of symptomatic SARS-CoV-2 infections | within 12 months after vaccination | Symptomatic SARS-CoV-2 infections will be defined by the presence of at least one symptom amongst fever, dyspnea, cough, chest pain, anosmia, ageusia, diarrhea or vomiting, AND a positive SARS-CoV-2 PCR, |
| Anti-nucleocapsid IgG levels | between 21 and 28 days from the first dose | — |
Countries
France
Outcome results
None listed