Transplant Complication
Conditions
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
Interventions
DRUGPooled allogeneic fecal microbiotherapy
Capsule for oral use
DRUGPlacebo
Capsule for oral use
Sponsors
MaaT Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 12 months post alloHCT | To compare the efficacy of MaaT033 with its placebo on OS at 12 months after alloHCT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Restoration of gut microbiota diversity | 12 months post alloHCT | To evaluate MaaT033 efficacy in gut microbiota diversity restoration using alpha-diversity (Richness index) |
| 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 |
| Quality of life questionnaire | 12 months post alloHCT | To evaluate the Quality of Life (EORTC QLQ C30 questionnaire) |
Countries
Belgium, France, Germany, Netherlands, Spain, United Kingdom
Contacts
Primary ContactEmilie Plantamura, PharmD, PhD
Backup ContactRomain Collard
Outcome results
None listed