Oral Pooled Fecal Microbiotherapy to Prevent Allogeneic Hematopoietic Cell Transplantation Complications (PHOEBUS Trial)
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Oral pooled fecal microbiotherapy - MaaT033 3 capsules per day |
Drug: Pooled allogeneic fecal microbiotherapy
Capsule for oral use
Other Names:
|
| Placebo Comparator: Placebo capsule 3 capsules per day |
Drug: Placebo
Capsule for oral use
|
Outcome Measures
Primary Outcome Measures
- 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
- Restoration of gut microbiota diversity [12 months post alloHCT]
To evaluate MaaT033 efficacy in gut microbiota diversity restoration using alpha-diversity (Richness index)
- 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
- 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
- Infectious-related mortality [12 months post alloHCT]
To evaluate the cumulative incidence of infectious-related 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
- 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 (EORTC QLQ C30 questionnaire)
- 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
- 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
- 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
- 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
Eligibility Criteria
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
-
- high dose cyclophosphamide)
-
Patients receiving a manipulated graft (in-vitro T-cell depletion)
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Patients planned to receive a conditioning regimen with alemtuzumab
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Patients planned to receive alloHCT with cord blood cells
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Patients planned to receive alloHCT from unrelated donor with >= 3/10 HLA-mismatches
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Patients receiving a large spectrum antibiotic at time of randomization
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Patients planned to receive vedolizumab or abatacept for GvHD prophylaxis
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Creatinine clearance <30 mL/min
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Bilirubin or amino-transferases abnormalities contra-indicating alloHCT
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Cardiac ejection fraction less than 40%
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Pulmonary impairment with <50% lung carbon monoxide diffusing capacity (DLCO)
-
Pregnancy
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Confirmed or suspected intestinal ischemia
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Confirmed or suspected toxic megacolon or gastrointestinal perforation
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Any history of gastro-intestinal surgery in the past 3 months
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Any history of chronic digestive disease (Crohn's disease, ulcerative colitis, inflammatory bowel disease or other relevant digestive condition according to physician's judgement)
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Known allergy or intolerance to trehalose or maltodextrin
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Patients with EBV-IgG negative serology
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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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- MaaT Pharma
Investigators
- Principal Investigator: Florent Malard, MD, PhD, APHP
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MPOH08