Hematologic Diseases, Chemotherapy Effect
Conditions
Keywords
microbiota, microbiotherapy
Brief summary
Richness and diversity of gut microbiota are increasingly found to be associated with cancer outcomes. Moreover, an adequately responsive immune system seems to rely on the existence of a functioning gut ecosystem that includes the microbiota and its natural environment. Cancer by itself, but also cancer treatments - in particular chemotherapy - induce gut dysbiosis, impair the constant reparation mechanisms of the gut epithelium, disrupt immune homeostasis, and stunt immune responsiveness. The objective of MaaT033 is to (1) prevent the decay of the gut ecosystem (dysbiosis) to preserve immune homeostasis, (2) restore and optimize the gut ecosystem to full functionality including its role in repairing the gut epithelium and healthy gut barrier, and (3) maintain a restored gut ecosystem and fully functional immune homeostasis. Restoring the full gut ecosystem and its associated microbiota could become an important therapeutic option to improve clinical outcomes and control adverse events of conventional approaches, including immunotherapy in cancer patients. As a first step, MaaT033 capsules containing lyophilized, pooled, full-ecosystem microbiota in its natural environment are to be tested for their safety and tolerability in hematological malignant patients, who are exposed to intensive rounds of chemotherapy and antibiotics.
Interventions
DRUGMaaT033 capsule
Oral capsule
Sponsors
MaaT Pharma
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
3+3 design dose escalation
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or Female 2. Age ≥ 18 years 3. Patients diagnosed with AML defined according to WHO 2016 criteria with ≥20% leukemic blasts in the bone marrow or with high- risk myelodysplastic syndrome, receiving intensive chemotherapy 4. Patients healthy enough to likely receive their consolidation or second cycle of chemotherapy after induction chemotherapy 5. Patients healthy enough to likely receive HSCT 6. Informed written consent 7. Patient recovered from neutropenia
Exclusion criteria
1. Acute promyelocytic leukemia (AML-M3) 2. AML secondary to myeloproliferative disorder or chronic myelomonocytic leukemia (CMML) 3. Acute myeloid leukemia BCR-ABL1+ 4. Active CNS leukemia 5. Patients with a life expectancy of \<70 days according to investigator's opinion, or subject to therapeutic limitations 6. Confirmed or suspected intestinal ischemia 7. Confirmed or suspected toxic megacolon or gastrointestinal perforation 8. Active uncontrolled infection according to the attending physician 9. Any gastro-intestinal bleeding in the past 3 months 10. Any history of gastro-intestinal surgery in the past 3 months 11. Any history of inflammatory bowel disease 12. Any counter-indication to swallow capsules 13. Enrollment in another trial that may interfere with this study 14. Known allergy or intolerance to trehalose, maltodextrin or PEG 15. Women of childbearing potential without efficient contraceptive protection 16. Pregnant or breastfeeding 17. Patients with EBV-negative serology 18. Subject who, in the judgment of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development; 19. Exclusion period of a previous study 20. Administrative or legal supervision 21. Confirmed positive result to SARS-CoV-2 nasopharyngeal test at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of MaaT033-related, treatment-emergent (serious) adverse events, grade >3, as assessed by CTCAE v4.0 | From treatment start (V1, end of aplasia) to the end of the study (end of consolidation or up to 10 weeks) | Evaluation of safety and tolerability of MaaT033 in patients with hematologic malignancies |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose regimen evaluation | From treatment start (V1, end of aplasia) to the end of the study (end of consolidation or up to 10 weeks) | Activity assessment of the different dose regimens defined as bacterial engraftment of the product |
Countries
France
Outcome results
None listed