E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patient who underwent Allogeneic hematopoietic stem cell transplantation (allo-HSCT) for various haematological malignancies. Faecal microbiota transplantation (FMT) will be assessed to prevent allogeneic complications such as graft-versus-host disease (GvHD) and infection which remain a major cause of morbidity, mortality, and impaired quality of life. During the conditioning regimen and after the allo-HSCT, many treatments can negatively impact microbiota homeostasis. |
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E.1.1.1 | Medical condition in easily understood language |
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) for malignant hemopathy to prevent post-allogeneic complications such as graft versus host disease and infections. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
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 effect of allogeneic FMT compared with no treatment on graft-versus-host disease-free, relapse-free survival (GRFS) at one year post-transplant in patients treated with myeloablative conditioning (MAC) allo-HSCT for haematological malignancy. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate incidence of engraftment, incidence of aGvHD and cGvHD, overall survival, progression-free survival, transplant-related mortality, quality of life, rate of severe infections.
• To evaluate the tolerance and safety of post-allo-HSCT FMT, its effect on multidrug-resistant bacteria/extended spectrum beta-lactamases (ESBL), the cumulative incidence of clostridium difficile infection and diarrhoea.
• To evaluate microbiota composition and diversity by 16s sequencing prospectively in all patients (treatment group and control group) before allo-HSCT, before FMT and at M1, M3 and M12, and in donors.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients who underwent allo-HSCT for a controlled haematological malignancy.
• Patients aged ≥ 18 years old.
• Patients affiliated with a social security organization.
• Patients who had signed informed consent.
• Allo-HSCT procedure: MAC followed by a granulocyte-colony stimulating factor mobilized-peripheral HSC graft infusion.
• Any HSCT donor, except cord blood.
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E.4 | Principal exclusion criteria |
• Medical history of another progressive uncontrolled cancer within the previous three years.
• Presence of a simultaneous serious and uncontrolled disease.
• Faecal incontinence.
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E.5 End points |
E.5.1 | Primary end point(s) |
Graft-versus-host disease-free, relapse-free survival (GRFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Incidence of engraftment
- Incidence of aGvHD
- Incidence of cGvHD
- Overall survival
- Progression-free survival
- Transplant-related mortality
- Quality of life
- Rate of severe infections
- Tolerance and safety of post-allo-HSCT FMT
- Effect on multidrug-resistant bacteria/extended spectrum beta-lactamases (ESBL)
- Cumulative incidence of clostridium difficile infection and diarrhoea
- Microbiota composition and diversity by 16s sequencing prospectively in all patients (treatment group and control group) and in donors.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Rate of engraftment at day 100
- Cumulative incidence of grade II-IV acute GvHD at 1 year
- Cumulative incidence of chronic GvHD at 2 years
- Overall survival and progression-free survival at 1 and 2 years
- Transplant related mortality at six months, 1 and 2 years.
- Quality of life at inclusion, M1, M3, M6, M12 and M24.
- Cumulative incidence of infectious disease at 1 year
- Tolerance and safety after allo-HSCT
- Effect on multidrug-resistant bacteria and ESBL at 1 year
- Cumulative incidence of clostridium difficile infection at 1 year
- Cumulative incidence of diarrhoea at 6 months
- Microbiota composition and diversity assessed by 16s sequencing performed prospectively in all patients (before allo-HSCT, before FMT, and at M1, M3 and M12 post FMT) and in donors
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
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.8.3 |
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 | 23 |
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 | Yes |
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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An independent data monitoring committee is planned. This committee will convene at study start-up and then as and when needed throughout the study, at its own initiative or at the request of the sponsor, to analyse safety data. It will have a consultative role on any move to stop the trial prematurely for toxicity. This committee includes a haematologist, a pharmacist, and a biostatistician not participating in the study. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |