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

Phase 2

Recruiting

• Conditions: Transplant Complication
• Interventions: Drug: Pooled allogeneic fecal microbiotherapy; Drug: Placebo

• Registration Number: NCT05762211
• Lead Sponsor: MaaT Pharma

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-01-27
• Study First Submitted QC: 2023-02-27
• Study First Posted: 2023-03-09
• Study Start: 2023-10-31
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-20
• Last Update Posted: 2024-12-27
• Primary Completion: 2026-10-31
• Study Completion: 2027-02-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 387

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oral pooled fecal microbiotherapy - MaaT033	Pooled allogeneic fecal microbiotherapy	3 capsules per day
Placebo capsule	Placebo	3 capsules per day

Primary Outcome Measures

Name	Time	Method
Overall survival	12 months post alloHCT	To compare the efficacy of MaaT033 with its placebo on OS at 12 months after alloHCT

Secondary Outcome Measures

Name	Time	Method
Proportion of patients who have discontinued immune suppression therapies	12 months after alloHCT	To evaluate the proportion of patients who have discontinued immune suppression therapies including standard of care GvHD prophylaxis and steroid treatment
GRFS	12 months post alloHCT	To evaluate GvHD-free relapse-free survival (GRFS) at 12 months after alloHCT
Quality of life questionnaire	12 months post alloHCT	To evaluate the Quality of Life (FACT-BMT questionnaire)
Proportion of patients with severe infections	6 months after alloHCT	To evaluate the proportion of patients with severe infections defined by NCI-CTCAE ≥ Grade 3 within 6 months after alloHCT
Restoration of gut microbiota diversity	12 months post alloHCT	To evaluate MaaT033 efficacy in gut microbiota diversity restoration using alpha-diversity (Richness index)
grade 3-4 acute GvHD	12 months post alloHCT	To evaluate the cumulative incidence of grade 3-4 severe acute GvHD within 12+; + months after alloHCT
Non-relapse mortality	12 months post alloHCT	To evaluate the cumulative incidence of non-relapse mortality within 12 months after alloHCT
GvHD-related mortality	12 months post alloHCT	To evaluate the cumulative incidence of GvHD-related mortality within 12 months after alloHCT
Time to platelet engraftment	12 months after alloHCT	Time to the first of 3 consecutive days of absolute neutrophil counts ≥ 0.5 G/L after alloHCT
grade 2-4 acute GvHD	6 months post alloHCT	To evaluate the cumulative incidence of grade 2-4 acute GvHD within 6 months after alloHCT
Time to neutrophil engraftment	12 months after alloHCT	Time to the first of 3 consecutive days of platelet counts ≥ 20 G/L after alloHCT
Safety: incidence of AEs	12 months after alloHCT	To evaluate MaaT033 safety
Infectious-related mortality	12 months post alloHCT	To evaluate the cumulative incidence of infectious-related mortality within 12 months after alloHCT

Trial Locations

Locations (54)

Universitair Ziekenhuis Antwerpen; 🇧🇪 Antwerpen, Belgium

AZ Sint - Jan Brugge; 🇧🇪 Brugge, Belgium

Institut Jules Bordet; 🇧🇪 Brussel, Belgium

Universitair Ziekenhuis Brussel; 🇧🇪 Brussel, Belgium

Universitair Ziekenhuis Gent; 🇧🇪 Gent, Belgium

Cliniques Universitaires Saint-Luc; 🇧🇪 Louvain, Belgium

Algemeen Ziekenhuis Delta - Campus Rumbeke; 🇧🇪 Roeselare, Belgium

CHU Besançon; 🇫🇷 Besançon, France

CHRU Lille; 🇫🇷 Lille, France

Centre Hospitalier Universitaire Limoges; 🇫🇷 Limoges, France

Hôpital Saint-Eloi; 🇫🇷 Montpellier, France

Hôpital l'Archet; 🇫🇷 Nice, France

Hôpital Saint-Louis; 🇫🇷 Paris, France

Centre Hospitalier Lyon-Sud; 🇫🇷 Pierre-Bénite, France

Centre Hospitalier Universitaire de Poitiers; 🇫🇷 Poitiers, France

Centre Hospitalier Régional Universitaire de Tours; 🇫🇷 Tours, France

CHU Tours; 🇫🇷 Tours, France

Universitätsklinikum Augsburg; 🇩🇪 Augsburg, Germany

Helios Klinikum Berlin-Buch; 🇩🇪 Berlin, Germany

Universitätsklinikum Essen; 🇩🇪 Essen, Germany

Universitätsklinikum Frankfurt; 🇩🇪 Frankfurt, Germany

Universitätsklinikum des Saarlandes; 🇩🇪 Hombourg, Germany

Universitätsklinikum Schleswig-Holstein - Campus Kiel; 🇩🇪 Kiel, Germany

Universitätsklinikum Leipzig; 🇩🇪 Leipzig, Germany

Universitätsmedizin Mannheim; 🇩🇪 Mannheim, Germany

Klinikum rechts der Isar der Technischen Universität; 🇩🇪 München, Germany

Universitair Medisch Centrum Groningen; 🇳🇱 Groningen, Netherlands

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Universitari Vall d'Hebrón; 🇪🇸 Barcelona, Spain

Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet); 🇪🇸 Barcelona, Spain

Hospital Universitario Virgen de las Nieves; 🇪🇸 Granada, Spain

Hospital General Universitario Gregorio Marañón; 🇪🇸 Madrid, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Universitario Puerta de Hierro - Majadahonda; 🇪🇸 Majadahonda, Spain

Hospital General Universitario Morales Meseguer; 🇪🇸 Murcia, Spain

Clinica Universidad de Navarra - Pamplona; 🇪🇸 Pamplona, Spain

Complejo Asistencial Universitario de Salamanca - Hospital Clínico; 🇪🇸 Salamanca, Spain

Hospital Universitario Marques de Valdecilla; 🇪🇸 Santander, Spain

Hospital Universitario Virgen del Rocío; 🇪🇸 Sevilla, Spain

Hospital Clínico Universitario de Valencia Avenida Blasco Ibáñez; 🇪🇸 Valencia, Spain

Hospital Universitario La Fe; 🇪🇸 Valencia, Spain

Cardiff and Vale University Health Board; 🇬🇧 Cardiff, United Kingdom

CHU Angers; 🇫🇷 Angers, France

CHU Caen; 🇫🇷 Caen, France

CHU Grenoble; 🇫🇷 La Tronche, France

Institut Paoli Calmettes; 🇫🇷 Marseille, France

CHU Nantes Hôtel Dieu; 🇫🇷 Nantes, France

Hôpital St Antoine; 🇫🇷 Paris, France

Hôpital Haut-Lévêque; 🇫🇷 Pessac, France

CHU Rennes - Hôpital Pontchaillou; 🇫🇷 Rennes, France

CHU St Etienne; 🇫🇷 Saint-Priest-en-Jarez, France

IUCT Toulouse; 🇫🇷 Toulouse, France

Universitätsklinikum Bonn; 🇩🇪 Bonn, Germany

Universitätsklinikum Ulm; 🇩🇪 Ulm, Germany