Clinical trial NCT05762211: Oral Pooled Fecal Microbiotherapy to Prevent Allogeneic Hematopoietic Cell Transplantation Complications (PHOEBUS Trial)
Official title: A Multi-center Randomized, Double Blinded Phase IIb Trial Evaluating Oral Pooled Fecal Microbiotherapy MaaT033 to Prevent Allogeneic Hematopoietic Cell Transplantation Complications (PHOEBUS Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Transplant Complication
Lead sponsor: MaaT Pharma
Sponsor class: INDUSTRY
First posted: 2023-03-09
Enrollment: 387
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Overall survival
timeFrame: 12 months post alloHCT
Secondary outcomes:
measure: Restoration of gut microbiota diversity
timeFrame: 12 months post alloHCT
measure: grade 2-4 acute GvHD
timeFrame: 6 months post alloHCT
measure: grade 3-4 acute GvHD
timeFrame: 12 months post alloHCT
measure: Non-relapse mortality
timeFrame: 12 months post alloHCT
measure: Infectious-related mortality
timeFrame: 12 months post alloHCT
measure: GvHD-related mortality
timeFrame: 12 months post alloHCT
measure: GRFS
timeFrame: 12 months post alloHCT
measure: Quality of life questionnaire
timeFrame: 12 months post alloHCT
measure: Quality of life questionnaire
timeFrame: 12 months post alloHCT
measure: Proportion of patients with severe infections
timeFrame: 6 months after alloHCT
measure: Proportion of patients who have discontinued immune suppression therapies
timeFrame: 12 months after alloHCT
measure: Time to platelet engraftment
timeFrame: 12 months after alloHCT
measure: Time to neutrophil engraftment
timeFrame: 12 months after alloHCT
measure: Safety: incidence of AEs
timeFrame: 12 months after alloHCT
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Brugge
country: Belgium
facility: AZ Sint - Jan Brugge
city: Brussel
country: Belgium
facility: Institut Jules Bordet
city: Brussel
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Louvain
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Roeselare
country: Belgium
facility: Algemeen Ziekenhuis Delta - Campus Rumbeke
city: Angers
country: France
facility: CHU Angers
city: Besançon
country: France
facility: CHU Besançon
city: Caen
country: France
facility: CHU Caen
city: La Tronche
country: France
facility: CHU Grenoble
city: Lille
country: France
facility: CHRU Lille
city: Limoges
country: France
facility: Centre Hospitalier Universitaire Limoges
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: Hôpital Saint-Eloi
city: Nantes
country: France
facility: CHU Nantes Hôtel Dieu
city: Nice
country: France
facility: Hôpital l'Archet
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hôpital St Antoine
city: Pessac
country: France
facility: Hôpital Haut-Lévêque
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon-Sud
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitiers
city: Rennes
country: France
facility: CHU Rennes - Hôpital Pontchaillou
city: Saint-Priest-en-Jarez
country: France
facility: CHU St Etienne
city: Toulouse
country: France
facility: IUCT Toulouse
city: Tours
country: France
facility: Centre Hospitalier Régional Universitaire de Tours
city: Tours
country: France
facility: CHU Tours
city: Augsburg
country: Germany
facility: Universitätsklinikum Augsburg
city: Berlin
country: Germany
facility: Helios Klinikum Berlin-Buch
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Hombourg
country: Germany
facility: Universitätsklinikum des Saarlandes
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein - Campus Kiel
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim
city: München
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
city: Murcia
country: Spain
facility: Hospital General Universitario Morales Meseguer
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca - Hospital Clínico
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia Avenida Blasco Ibáñez
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Cardiff
country: United Kingdom
facility: Cardiff and Vale University Health Board
Study officials:
affiliation: APHP
name: Florent Malard, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: