Safety and Tolerability Evaluation of MaaT033

Study Overview
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Brief Summary
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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.

Official Title
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Safety Phase I Evaluation of MaaT033, a Lyophilized Full-ecosystem Gut Microbiota Delayed-release Capsule, In HeMatOlogy Malignant Patients Under iNtensive Chemotherapy (CIMON)

Conditions
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Hematologic Diseases, Chemotherapy Effect

Intervention / Treatment
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* Drug: MaaT033 capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female Age ≥ 18 years 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 Patients healthy enough to likely receive their consolidation or second cycle of chemotherapy after induction chemotherapy Patients healthy enough to likely receive HSCT Informed written consent Patient recovered from neutropenia Exclusion Criteria: Acute promyelocytic leukemia (AML-M3) AML secondary to myeloproliferative disorder or chronic myelomonocytic leukemia (CMML) Acute myeloid leukemia BCR-ABL1+ Active CNS leukemia Patients with a life expectancy of <70 days according to investigator's opinion, or subject to therapeutic limitations Confirmed or suspected intestinal ischemia Confirmed or suspected toxic megacolon or gastrointestinal perforation Active uncontrolled infection according to the attending physician Any gastro-intestinal bleeding in the past 3 months Any history of gastro-intestinal surgery in the past 3 months Any history of inflammatory bowel disease Any counter-indication to swallow capsules Enrollment in another trial that may interfere with this study Known allergy or intolerance to trehalose, maltodextrin or PEG Women of childbearing potential without efficient contraceptive protection Pregnant or breastfeeding Patients with EBV-negative serology 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; Exclusion period of a previous study Administrative or legal supervision Confirmed positive result to SARS-CoV-2 nasopharyngeal test at screening

Ages Eligible for Study
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Minimum Age: 18 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: Supportive Care
Intervention Model: Sequential Assignment
Interventional Model Description: 3+3 design dose escalation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MaaT033 treatment<br>A Lyophilized Full-ecosystem Gut Microbiota Delayed-release Capsule | Drug: MaaT033 capsule<br>* Oral capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of MaaT033-related, treatment-emergent (serious) adverse events, grade >3, as assessed by CTCAE v4.0 | Evaluation of safety and tolerability of MaaT033 in patients with hematologic malignancies | From treatment start (V1, end of aplasia) to the end of the study (end of consolidation or up to 10 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose regimen evaluation | Activity assessment of the different dose regimens defined as bacterial engraftment of the product | From treatment start (V1, end of aplasia) to the end of the study (end of consolidation or up to 10 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microbiota, microbiotherapy