E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
E.1.1.1 | Medical condition in easily understood language |
Vaccination against Streptococcus pneumoniae is recommended in patients treated with chemotherapy |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046859 |
E.1.2 | Term | Vaccination |
E.1.2 | System Organ Class | 100000004865 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039244 |
E.1.2 | Term | Routine vaccination |
E.1.2 | System Organ Class | 100000004865 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the immunogenicity of the combined pneumococcal vaccination strategy (one injection of PCV13 followed 2 months later by an injection of PPV23) 1 month after the complete vaccination regimen in adult subjects treated with cytotoxic chemotherapy for AML or lymphoma.
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E.2.2 | Secondary objectives of the trial |
- Evaluation of the immunological response after PCV13 injection at 4 weeks. - Evaluation of the durability of the immunological response at 3-6 months after injection of PPV23. - Evaluation of the durability of the immunological response of the combined vaccination strategy at 9-12 months after the injection of PPV23 - 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 and correlation them with the response to vaccination as determined by the reference method. - Determination of early and late pneumococcal vaccine response factors in the AML and lymphoma population. - Evaluation of the clinical tolerability and safety of the combined vaccination strategy in the AML and lymphoma population. - Evaluation of the concordance between the reference test (WHO ELISA) and an industrial kit (Vacczyme® Binding Site®).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patient ≥ 18 year-old. - AND medical follow-up in hematology unit - AND had received a first course of chemotherapy for acute myeloblastic leukemia without PML-RARa and no planned allogeneic hematopoietic stem cell transplantation or for diffuse large B cell lymphoma or for follicular lymphoma - Life expectancy > 6 months - Having signed the consent form. - Having an health insurance.
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E.4 | Principal exclusion criteria |
Receiving monoclonal antibodies or biotherapies altering the immune response, other than anti-CD20 antibodies in the chemotherapy protocol. - Previous vaccination with PCV13 or PPV23 (unless PCV13 was administered in childhood. The last injection must be performed at least five years ago). - 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. - Patient who already received chemotherapy for malignancy in the previous 2 years before the inclusion. - Allogeneic hematopoietic stem cell transplantation planned in the following 3 months after the first chemotherapy course. - Curative anticoagulation within 7 days before vaccination. - Major blood clotting disorders preventing intramuscular injection. - Medical history of anaphylactic reaction to vaccination. - Known allergy to one of the vaccine components. - Involvement to another vaccine biomedical research. - Protected person. - Pregnant women or women of childbearing age without appropriate contraceptive measures. - Perfusion of polyvalent immunoglobulins during follow-up.
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients having a good response to combined strategy at 4 weeks after the end of the combined strategy. A good response to vaccination is defined by 4/7 tested serotypes responding to these 4 criteria: a serotype-specific IgG titer ≥ 1μg/L (WHO threshold), a two-fold increase of this IgG titer compare to baseline before vaccination, a serotype-specific OPA ≥1/8, and a four-fold increase of functional antibodies compare to baseline. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at 4-6 weeks after the end of the combined strategy |
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E.5.2 | Secondary end point(s) |
1-Proportion of patients having an ELISA serotype-specific IgG titer ≥ 1μg/L (WHO threshold) and a two-fold increase of this IgG titer compared to baseline at 4 weeks after the PCV13 injection. 2-Proportion of patients having a sustainable response to vaccination defined by an ELISA serotype-specific IgG titer ≥ 1μg/L (WHO threshold) and a two-fold increase of this IgG titer compared to baseline between 3-6 months after the PPV23 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. 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 injection. A significant increase is defined by a 4-fold increase of IgG and IgG2 titers, a 13-fold increase of IgA titers, and a 20-fold increase of IgM titers compared to baseline at inclusion. 5-To determine predictive factors for non-response to vaccination at 4weeks, and 9-12 months after PPV23 injection such as age, hematological malignancy, immune status, chemotherapy, immunotherapy. 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®).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-at 4 weeks after the PCV13 injection. 2-3-6 months after the PPV23 injection 3-9-12 months after the PPV23 injection. 4-4weeks after PCV13, and 4 weeks, 3-6 months and 9-12 months after PPV23 injection 5-4 weeks, and 9-12 months after PPV23 injection 6-9-12 months after PPV23 injection 7-12 months after PPV23 injection |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 39 |
E.8.9.1 | In the Member State concerned days | |