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

Study Overview
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Brief Summary
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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

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

Conditions
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Transplant Complication

Intervention / Treatment
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* Drug: Pooled allogeneic fecal microbiotherapy
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral pooled fecal microbiotherapy - MaaT033<br>3 capsules per day | Drug: Pooled allogeneic fecal microbiotherapy<br>* Capsule for oral use<br>* Other names: MaaT033;|
| Placebo Comparator: Placebo capsule<br>3 capsules per day | Drug: Placebo<br>* Capsule for oral use<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | To compare the efficacy of MaaT033 with its placebo on OS at 12 months after alloHCT | 12 months post alloHCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Restoration of gut microbiota diversity | To evaluate MaaT033 efficacy in gut microbiota diversity restoration using alpha-diversity (Richness index) | 12 months post alloHCT | 
| grade 2-4 acute GvHD | To evaluate the cumulative incidence of grade 2-4 acute GvHD within 6 months after alloHCT | 6 months post alloHCT | 
| grade 3-4 acute GvHD | To evaluate the cumulative incidence of grade 3-4 severe acute GvHD within 12+ + months after alloHCT | 12 months post alloHCT | 
| Non-relapse mortality | To evaluate the cumulative incidence of non-relapse mortality within 12 months after alloHCT | 12 months post alloHCT | 
| Infectious-related mortality | To evaluate the cumulative incidence of infectious-related mortality within 12 months after alloHCT | 12 months post alloHCT | 
| GvHD-related mortality | To evaluate the cumulative incidence of GvHD-related mortality within 12 months after alloHCT | 12 months post alloHCT | 
| GRFS | To evaluate GvHD-free relapse-free survival (GRFS) at 12 months after alloHCT | 12 months post alloHCT | 
| Quality of life questionnaire | To evaluate the Quality of Life (EORTC QLQ C30 questionnaire) | 12 months post alloHCT | 
| Quality of life questionnaire | To evaluate the Quality of Life (FACT-BMT questionnaire) | 12 months post alloHCT | 
| Proportion of patients with severe infections | To evaluate the proportion of patients with severe infections defined by NCI-CTCAE ≥ Grade 3 within 6 months after alloHCT | 6 months after alloHCT | 
| Proportion of patients who have discontinued immune suppression therapies | To evaluate the proportion of patients who have discontinued immune suppression therapies including standard of care GvHD prophylaxis and steroid treatment | 12 months after alloHCT | 
| Time to platelet engraftment | Time to the first of 3 consecutive days of absolute neutrophil counts ≥ 0.5 G/L after alloHCT | 12 months after alloHCT | 
| Time to neutrophil engraftment | Time to the first of 3 consecutive days of platelet counts ≥ 20 G/L after alloHCT | 12 months after alloHCT | 
| Safety: incidence of AEs | To evaluate MaaT033 safety | 12 months after alloHCT |