Steroid refractory gastro-intestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation
Conditions
Interventions
Product Name: MaaT013
Product Code: 7P010
Pharmaceutical Form: Rectal suspension
Current Sponsor code: MaaT013
Concentration unit: g gram(s)
Concentration type: range
Concentration number: 30-90
Sponsors
MaaT Pharma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients who develop a first episode of Grade III or IV aGVHD (= gastrointestinal Stages 2 to 4) with gut predominance if other organs involved (Przepiorka D, 1995), resistant to a first-line therapy with steroids, defined as any of the following: a. Lack of improvement after 5 to 7 days of treatment with CS at 2mg/kg/d methylprednisolone equivalent dose. b. Progression after 3 days of treatment with CS at 2 mg/kg/d methylprednisolone equivalent dose. c. Patients treated with 1 mg/kg/d of CS because the physician deemed they would not tolerate 2 mg/kg/d and who correspond to the definition of SR patients. 2. Age = 18 years old 3. Allo-HSCT with any type of donor, stem cell source, GVHD prophylaxis or conditioning regimen 4. Patients able to have a minimum of 12 hours discontinuation of systemic antibiotics in order to perform the allogeneic FMT (for patients who require antibiotics, using antibiotics that have limited impact on the gut microbiota should be considered in priority. The complete list of recommended and not recommended antibiotics is in Appendix 6) 5. Signature of informed and written consent by the subject or by the subject’s legally acceptable representative for patients under guardianship or trusteeship Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
Exclusion criteria: 1. Grade IV hyper-acute GVHD as defined by the MD Anderson’s criteria (Saliba RM, 2007) 2. Late-onset aGVHD as defined by the NIH Consensus Criteria (Jagasia MH, 2015) 3. Overlap chronic GVHD as defined by the NIH Consensus Criteria (Jagasia MH, 2015) 4. Acute GVHD after donor lymphocytes infusion (DLI) 5. Relapsed/persistent malignancy requiring rapid immune suppression withdrawal 6. Active uncontrolled infection according to the attending physician 7. Current or past veno-occlusive disease or other uncontrolled complication unless otherwise agreed in writing by the sponsor. 8. Systemic drugs other than corticosteroids for GvHD treatment, including extra-corporeal photopheresis (ECP), unless treatments began before or concomitantly with corticosteroid treatment. New therapies after corticosteroids are a definitive non-inclusion criterium. Drugs for GVHD prevention (e.g., calcineurin inhibitors, Mycophenolate mofetil (MMF), ECP…), are allowed as long as treatment began before or concomitantly with the corticosteroid treatment. 9. Absolute neutrophil count < 0.5 x 109 /L 10. Absolute platelet count < 10 000 11. Patient with negative IgG EBV serology 12. Current or past evidence of toxic megacolon, bowel obstruction or gastrointestinal perforation on abdominal X-ray 13. Known allergy or intolerance to trehalose or maltodextrin 14. Vulnerable patients such as: minors, persons deprived of liberty, persons in Intensive Care Unit unable to provide informed consent prior to the intervention 15. Pregnancy: positive urinary or blood test in females of childbearing potential; lactation; absence of effective contraceptive method for females of childbearing potential throughout the entire duration of the study 16. Other ongoing interventional protocol that might interfere with the current study’s primary endpoint.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluation of the gastrointestinal response (Complete Response (CR) and Very Good Partial Response (VGPR)) at D28 of steroid refractory (SR) gastro-intestinal (GI) acute graft-versus-host disease (aGVHD) patients treated with allogeneic Fecal Microbiota Transfer (FMT).;Secondary Objective: •Evaluation of overall aGVHD response (CR and VGPR) •Evaluation of overall and best response rates (CR, VGPR and Partial Response (PR)) for GI and overall aGVHD •Evaluation of the durable overall response rate •Evaluation of the duration of response •Evaluation of safety within 24 hours after FMT as well as overall safety. •Evaluation of feasibility of allogeneic FMT procedure and acceptance by the patient •Evaluation of clinical safety and performance of MaaT Pharma’s medical device •Evaluation of the number of patients receiving the full treatment sequence (3 FMTs) •Evaluation of FMT activity and/or impact on: -Steroid-free, progression-free survival, relapse of the initial disease, GVHD-free survival, GVHD and relapse-free survival, overall survival -Infectious disorders -Multi-Drug Resistant Bacteria (MDRB) carriage -Clinical symptoms of skin/liver aGVHD associated with SR-GI-aGVHD -Stool evaluation (volume of diarrhea, Bristol stool chart) -Quality of Life;Primary end point(s): Efficacy of FMT in the treatment of SR-GI-aGVHD at D28 post inclusion (V4): Number and proportion of patients achieving GI aGVHD response by D28, defined as Complete Response or Very Good Partial Response. ;Timepoint(s) of evaluation of this end point: D28 post inclusion (V4) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Efficacy of FMT in the treatment of overall aGVHD at D28 post inclusion (V4) 2) Evaluation of overall and best response rates (CR, VGPR and Partial Response (PR)) for both GI and overall aGVHD 3) Evaluation of the durable overall response rate 4) Evaluation of the duration of response 5) Safety of FMT in patients with SR-GI-aGVHD 6) Feasibility of allogeneic FMT procedure and acceptability by the Patient Number of patients receiving 3 FMTs 8) Clinical safety and performance of MaaT Pharma’s medical device (Directive 9342 CE, med dev 2.7.1) 9) Evaluation of FMT activity and/or impact on steroid-free, progression-free survival, relapse of the initial disease, GVHD-free survival, GVHD and relapse-free survival and overall survival 10) Evaluation of FMT activity and/or impact on infectious disorders 11) Evaluation of FMT activity and/or impact on MDRB carriage 12) Evaluation of FMT activity and/or impact on clinical symptoms of skin/liver aGVHD associated with SR-GI-aGVHD 13) Stool evaluation (volume of diarrhea, Bristol stool chart) 14) Evaluation of microbiota reconstitution 15) Chronic GVHD incidence and severity 16) Assessment of a microbiota signature (Exploratory) 17) Impact of FMT on the immune system (Exploratory);Timepoint(s) of evaluation of this end point: D28 post inclusion (V4), M3 (V5), M6 (V6) and M12 (V7) | — |
Countries
France, Germany, Italy, Poland, United Kingdom
Contacts
Public ContactEmilie Plantamura
MaaT Pharma
Outcome results
None listed