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

• ClinicalTrials.gov Identifier: NCT04969601
• Recruitment Status: Recruiting
• First Posted: July 20, 2021
• Last Update Posted: November 15, 2021
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

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 12 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 (≥12-15 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.

Condition or disease	Intervention/treatment	Phase
Acute Leukemia; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia	Biological: vaccine COMIRNATY® (BNT162b2)	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 150 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Dose finding, stratified on the age group (≥1-<2 years, ≥2-<5 years, ≥5-<12 years)
• Masking: None (Open Label)
• Primary Purpose: Prevention
• 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.
• Actual Study Start Date: September 29, 2021
• Estimated Primary Completion Date: May 29, 2022
• Estimated Study Completion Date: March 29, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Anti Covid with COMIRNATY® (BNT162b2) vaccine; Two injections of COMIRNATY® (BNT162b2) vaccine 21-28 days apart	Biological: vaccine 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

Outcome Measures

Primary Outcome Measures :

1. Dose limiting toxicity (DLT) [ Time Frame: 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.

2. co-primary endpoint: Increase in anti-Spike Immunoglobulin G (IgG) titer AND positive anti-Spike neutralizing test [ Time Frame: at 2 months from first dose ]

   Increase in anti-Spike IgG will be defined as four times or more increase in anti-Spike IgG titer AND positive neutralizing test (from 1/5 dilution). The patient will be considered as having a " significant seroconversion " to vaccination if these 2 efficacy criteria are present

   - If these 2 efficacy criteria are present, the patient is considered as having a " significant seroconversion " to vaccination

Secondary Outcome Measures :

1. Anti-Spike IgG levels [ Time Frame: between 21 and 28 days from first dose ]
2. Anti-Spike IgG levels [ Time Frame: at 6 months from first dose ]
3. Anti-Spike IgG levels [ Time Frame: at 12 months from the 1st dose ]
4. Anti-nucleocapsid IgG levels [ Time Frame: between 21 and 28 days from the first dose ]
5. Anti-nucleocapsid IgG levels [ Time Frame: 6 months from the first dose ]
6. Anti-nucleocapsid IgG levels [ Time Frame: 12 months from the first dose ]
7. Neutralization ability of anti-Spike IgG (in case of anti-Spike IgG detection) [ Time Frame: at 2 months from the first injection ]
8. Neutralization ability of anti-Spike IgG (in case of anti-Spike IgG detection) [ Time Frame: at 6 months from the first injection ]
9. Neutralization ability of anti-Spike IgG (in case of anti-Spike IgG detection) [ Time Frame: at 12 months from the first injection ]
10. Anti-SARS-CoV-2 T cell specific response (Elispot) [ Time Frame: at 2 months after the first injection ]
11. Anti-SARS-CoV-2 T cell specific response (Elispot) [ Time Frame: at 6 months after the first injection ]
12. Anti-SARS-CoV-2 T cell specific response (Elispot) [ Time Frame: at 12 months after the first injection ]
13. Positivity of SARS-CoV-2 polymerase chain reaction (PCR) in nasopharynx [ Time Frame: at 8 days ]
    Positivity of SARS-CoV-2 PCR in nasopharynx in case of infection
14. Positivity of SARS-CoV-2 PCR in nasopharynx [ Time Frame: at 15 days ]
    Positivity of SARS-CoV-2 PCR in nasopharynx in case of infection
15. Positivity of SARS-CoV-2 PCR in nasopharynx [ Time Frame: at 28 days from infection ]
    Positivity of SARS-CoV-2 PCR in nasopharynx in case of infection
16. Rate of symptomatic SARS-CoV-2 infections [ Time Frame: 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,
17. Genotype of the SARS-CoV-2 variant in case of infection [ Time Frame: within 12 months after vaccination ]
18. Time between chemotherapy planned date and effective date in case of infection [ Time Frame: within 12 months after vaccination ]
19. Covid19 World Health Organization (WHO) progression scale [ Time Frame: 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
20. SARS-CoV-2 PCR of the household (contact cases) [ Time Frame: within 12 months after vaccination ]
    In case of infection in a vaccinated child, SARS-CoV-2 PCR of the household (contact cases) from the diagnosis and within 7 days of contact, depending on the contagion (if 1st PCR is negative)

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 15 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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
  • With acute myeloid leukemia within 12 months from the end of treatment
• Healthy siblings aged 12 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

Exclusion Criteria:

• Documented SARS-CoV-2 infection ongoing or that occurred less than 3 months ago
• Known clinical allergy to polyethylene glycol (PEG)
• Pregnant woman during first pregnancy quarter or lactating woman
• Platelet <50 Giga(G) G/L or neutrophils <0.5 G/L at time of vaccination
• Vaccination within 4 weeks from the 1st injection or planning to receive an approved vaccine 4 weeks after the last 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

Contacts and Locations

Contacts

Contact: Arnaud PETIT, Pr; +331.71.73.82.57; arnaud.petit@aphp.fr

Contact: Matthieu RESCHE-RIGON, Pr; +33142499773; matthieu.resche-rigon@u-paris.fr

Locations

France

Hôpital Armand Trousseau; Recruiting

Paris, France, 75012

Contact: Arnaud Petit, Pr +331.44.73.53.14 arnaud.petit@aphp.fr

Hôpital Robert Debré; Not yet recruiting

Paris, France, 75019

Contact: Marion Strullu +331.87.89.16.11 marion.strullu@aphp.fr

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

More Information

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT04969601
• Other Study ID Numbers: APHP210639
• First Posted: July 20, 2021
• Last Update Posted: November 15, 2021
• Last Verified: November 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Acute Disease; Neoplasms by Histologic Type; Neoplasms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes