Oral Pooled Fecal Microbiotherapy to Prevent Allogeneic Hematopoietic Cell Transplantation Complications (PHOEBUS Trial)

Официальное название

A Multi-center Randomized, Double Blinded Phase IIb Trial Evaluating Oral Pooled Fecal Microbiotherapy MaaT033 to Prevent Allogeneic Hematopoietic Cell Transplantation Complications (PHOEBUS Trial)

Обзор

This randomized, placebo-controlled phase IIb study (PHOEBUS trial) aims to evaluate the activity of fecal microbiotherapy MaaT033 to improve survival through the prevention of transplant-related complications in eligible alloHCT patients

Вмешательства

• Препарат Pooled allogeneic fecal microbiotherapy
  Capsule for oral use
• Препарат Placebo
  Capsule for oral use

Первичные конечные точки

• Overall survival [Срок оценки: 12 months post alloHCT]

Вторичные конечные точки (12)

• Restoration of gut microbiota diversity [Срок оценки: 12 months post alloHCT]
• grade 2-4 acute GvHD [Срок оценки: 6 months post alloHCT]
• grade 3-4 acute GvHD [Срок оценки: 12 months post alloHCT]
• Non-relapse mortality [Срок оценки: 12 months post alloHCT]
• Infectious-related mortality [Срок оценки: 12 months post alloHCT]
• GvHD-related mortality [Срок оценки: 12 months post alloHCT]
• GRFS [Срок оценки: 12 months post alloHCT]
• Quality of life questionnaire [Срок оценки: 12 months post alloHCT]
• Quality of life questionnaire [Срок оценки: 12 months post alloHCT]
• Proportion of patients with severe infections [Срок оценки: 6 months after alloHCT]
• Proportion of patients who have discontinued immune suppression therapies [Срок оценки: 12 months after alloHCT]
• Time to platelet engraftment [Срок оценки: 12 months after alloHCT]

Критерии участия

Критерии включения

• Age ≥ 50 years old
• Presence of a hematologic malignancy for which an alloHCT is indicated with a reduced toxicity or reduced intensity conditioning regimen
• Patients with polynuclear neutrophils > 0.5 G/L
• Patients having received wide spectrum antibiotics within the last 90 days prior to inclusion
• Karnofsky index ≥ 70%
• Availability of a sibling donor, an unrelated stem-cell donor or a familial haploidentical donor
• Written informed consent

Критерии исключения

• Patients planned to receive a non-myeloablative conditioning regimen (2 Gray total body irradiation (TBI) +/- purine analog, fludarabine + cyclophosphamide or equivalent)
• Patients planned to receive a conventional myeloablative conditioning regimen (e.g. high dose cyclophosphamide and high dose TBI (≥10Gy); high dose busulfan (12.8 mg/kg IV) + high dose cyclophosphamide)
• Patients receiving a manipulated graft (in-vitro T-cell depletion)
• Patients planned to receive a conditioning regimen with alemtuzumab
• Patients planned to receive alloHCT with cord blood cells
• Patients planned to receive alloHCT from unrelated donor with >= 3/10 HLA-mismatches
• Patients receiving a large spectrum antibiotic at time of randomization
• Patients planned to receive vedolizumab or abatacept for GvHD prophylaxis
• Creatinine clearance <30 mL/min
• Bilirubin or amino-transferases abnormalities contra-indicating alloHCT
• Cardiac ejection fraction less than 40%
• Pulmonary impairment with <50% lung carbon monoxide diffusing capacity (DLCO)
• Pregnancy
• Confirmed or suspected intestinal ischemia
• Confirmed or suspected toxic megacolon or gastrointestinal perforation
• Any history of gastro-intestinal surgery in the past 3 months
• Any history of chronic digestive disease (Crohn's disease, ulcerative colitis, inflammatory bowel disease or other relevant digestive condition according to physician's judgement)
• Known allergy or intolerance to trehalose or maltodextrin
• Patients with EBV-IgG negative serology
• Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.
• Vulnerable patients such as: persons deprived of liberty, persons in Intensive Care Unit unable to provide informed consent prior to the intervention.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Франция · 20 центров

• CHU Angers — Angers
• CHU Besançon — Besançon
• CHU Caen — Caen
• CHU Grenoble — La Tronche
• CHRU Lille — Lille
• Centre Hospitalier Universitaire Limoges — Limoges
• Institut Paoli Calmettes — Marseille
• Hôpital Saint-Eloi — Montpellier
• … и ещё 12 центров

Испания · 14 центров

• Hospital de la Santa Creu i Sant Pau — Barcelona
• Hospital Universitari Vall d'Hebrón — Barcelona
• Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet) — Barcelona
• Hospital Universitario Virgen de las Nieves — Granada
• Hospital General Universitario Gregorio Marañón — Madrid
• Hospital Universitario La Paz — Madrid
• Hospital Universitario Puerta de Hierro - Majadahonda — Majadahonda
• Hospital General Universitario Morales Meseguer — Murcia
• … и ещё 6 центров

Германия · 11 центров

• Universitätsklinikum Augsburg — Augsburg
• Helios Klinikum Berlin-Buch — Berlin
• Universitätsklinikum Bonn — Bonn
• Universitätsklinikum Essen — Essen
• Universitätsklinikum Frankfurt — Frankfurt
• Universitätsklinikum des Saarlandes — Hombourg
• Universitätsklinikum Schleswig-Holstein - Campus Kiel — Kiel
• Universitätsklinikum Leipzig — Leipzig
• … и ещё 3 центра

Бельгия · 7 центров

• Universitair Ziekenhuis Antwerpen — Antwerp
• AZ Sint - Jan Brugge — Bruges
• Institut Jules Bordet — Brussels
• Universitair Ziekenhuis Brussel — Brussels
• Universitair Ziekenhuis Gent — Ghent
• Cliniques Universitaires Saint-Luc — Leuven
• Algemeen Ziekenhuis Delta - Campus Rumbeke — Roeselare

Нидерланды · 1 центр

• Universitair Medisch Centrum Groningen — Groningen

Великобритания · 1 центр

• Cardiff and Vale University Health Board — Cardiff

Идентификаторы

NCT: NCT05762211 · MPOH08

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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