HEMATOVAC-Immunogenicity of an Anti-pneumococcal Combined Vaccination (PCV13+PPV23 versus PREVENAR20) in Lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Poitiers

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

29 Jan 2021 → ongoing

Decision date (initial)

2024-10-17

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS FRANCE · CHU de Poitiers

External identifiers

EU CT number

2024-517288-22-01

EudraCT number

2020-002017-18

ClinicalTrials.gov

NCT04460235

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To compare the immunogenicity of the combined pneumococcal vaccination strategy (PCV13+ PPV23 (Cohort A)) with the new strategy recommended by HAS using a single injection of PREVENAR20 (Cohort B) in adult subjects treated with cytotoxic chemotherapy.

Secondary objectives 7

1. Compare the immunological responses of PCV13 at 4 weeks versus PREVENAR20.
2. Evaluation of the durability of the immunological response at 3-6 months after injection of PPV23 versus 5-8 months post PREVENAR20
3. Evaluation of the durability of the immunological response of the combined vaccination strategy at 9-12 months after the injection of PPV23 ersus 11-14 months post PREVENAR20
4. Study the pneumococcal IgA, IgM, IgG and IgG2 total IgG levels at 4 weeks after PCV13 injection, and at 4 weeks, 3-6 months and 9-12 months after PPV23 injection versus 4 weeks, 3 months, 5-8 months and 11-14 months post PREVENAR20 and correlation them with the response to vaccination as determined by the reference method
5. Determination of early and late pneumococcal vaccine response factors in the lymphoma population
6. Evaluation of the clinical tolerability and safety of the combined vaccination strategy in the lymphoma population
7. Evaluation of the concordance between the reference test (WHO ELISA) and an industrial kit (Vacczyme® Binding Site®

Conditions and MedDRA coding

Lymphoma

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patient ≥ 18 year-old
2. AND medical follow-up in hematology unit
3. AND had received a first course of chemotherapy for diffuse large B cell lymphoma or for follicular lymphoma
4. Life expectancy > 6 months
5. Negative pregnancy test
6. Having signed the consent form
7. Having an health insurance
8. Free subject, without guardianship, tutorship or subordination

Exclusion criteria 13

1. Receiving monoclonal antibodies or biotherapies altering the immune response, other than anti-CD20 antibodies in the chemotherapy protocol
2. Involvement to another vaccine research
3. Protected person
4. Pregnant women or women of childbearing age without appropriate contraceptive measures.
5. Perfusion of polyvalent immunoglobulins during follow-up.
6. Participants with hypersensitivity to aluminum phosphate, phenol or CRM197 protein, protein derived from Corynebacterium diphtheria
7. Uncontrolled bacterial, viral or fungal infection less than 7 days
8. Previous vaccination with PCV13 or PPV23 (unless PCV13 was administered in childhood. The last injection must be performed at least five years ago)
9. Preexisting condition that altered the immune response: splenectomy, HIV, primary or secondary immune deficiency, nephrotic syndrome, sickle cell anemia, autoimmune disorder, solid organ transplantation, immunosuppressive drugs or biotherapy not included in the chemotherapy
10. Patient who already received chemotherapy for malignancy in the previous 2 years before the inclusion
11. Major blood clotting disorders preventing intramuscular injection.
12. Medical history of anaphylactic reaction to vaccination
13. Known allergy to one of the vaccine components

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients responding to the combined vaccination strategy (PCV13 + PPV23) assessed 4 weeks after PPV23 vaccination compared with the PREVENAR20 single injection vaccination strategy assessed 3 months post-injection according to the level of anti-pneumococcal IgG

Secondary endpoints 7

1. Proportion of patients having an ELISA serotype-specific IgG titer ≥ 1.3μg/mL (WHO threshold) and a two-fold increase of this IgG titer compared to baseline at 4 weeks after the PCV13 injection or PREVENAR20
2. Proportion of patients having a sustainable response to vaccination defined by an ELISA serotype-specific IgG titer ≥ 1.3μg/mL and a two-fold increase of this IgG titer compared to baseline between 3-6 months after the PPV23 injection or 5-8 months after PREVENAR20 injection
3. Proportion of patients having a sustainable response to vaccination defined by the same criteria as the primary outcome and measured between 9-12 months after the PPV23 injection or 11-14 months after PREVENAR20 injection
4. Proportion of responding patients having titers of IgG, IgG2, IgM, and IgA rising significantly at 4 weeks after PCV13 injection, and 4 weeks, 3- 6 months and 9-12 months after PPV23 injectionor at 4 weeks, 3 months, 5-8 months, 11-14 months after PREVENAR20 injection.
5. To determine predictive factors for non-response to vaccination at 4weeks, and 6-12 months after PPV23 injection/11-14 months PREVENAR 20 such as age, hematological malignancy, immune status, chemotherapy,.....
6. Number of patients having local or general reactions to vaccination and number of invasive pneumococcal infections with a documented serotype considered as vaccination failure
7. To assess the concordance between the reference immuno-monitoring dosage (WHO ELISA) and another kit of dosage (Vacczyme® Binding Site®).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Poitiers

Sponsor organisation

Centre Hospitalier Universitaire De Poitiers

Address

2 Rue De La Miletrie

City

Poitiers

Postcode

86000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Poitiers

Contact name

Pr Mathieu PUYADE

Public contact point

Organisation

Centre Hospitalier Universitaire De Poitiers

Contact name

Pr Mathieu PUYADE

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications