Clinical trial NCT06724536: Interaction Between Gut Microbiota and TKIs in Defining the Clinical Outcomes of Patients With CML
Official title: Interaction Between Gut Microbiota and Tyrosine Kinase Inhibitors in Defining the Clinical Outcomes of Patients With Chronic Myeloid Leukemia
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Leukemia,Myeloid, Chronic
Keywords: chronic myeloid leukemia
gut
microbiota
tyrosine kinase inhibitors
Lead sponsor: University of Turin, Italy
Sponsor class: OTHER
Collaborators: name: Pfizer
name: Novartis
First posted: 2024-12-09
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All hematologic patients of the the Hematology Division of the AO Ordine Mauriziano di Torino with a diagnosis of Philadelphia positive Chronic Myeloid Leukemia (CML) will be included.

Brief summary: Gut microbiome (GM) is acquiring increasing importance in human health and disease. GM influences hematopoiesis and immune cells types differentiation. Patients with cancer are characterized by dysbiosis and compromised immunity. In the case of Chronic Myeloid Leukemia (CML), treatment with Tyrosine Kinase Inhibitors (TKIs) restores immunosurveillance; in particular deep molecular response (DMR) is associated with increased levels of NK and CD8+ Tcells. There is no literature on the effects of GM on CML outcomes. This project aims to identify a microbial signature associated with a higher probability of achieving DMR.

Detailed description: Philadelphia positive Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder originating from pluripotent hematopoietic cells. Treatment typically involves tyrosine-kinase inhibitors (TKIs), which have significantly improved long-term survival. While generally well-tolerated, TKIs can cause side effects, particularly gastrointestinal issues (diarrhea, constipation, abdominal pain, malabsorption, bleeding) and liver/pancreatic enzyme increases, which may persist and affect quality of life. Additionally, cardiovascular events, often linked to metabolic changes (e.g., glucose intolerance, diabetes, hypertension), occur more frequently during treatment. These side effects raise concerns about TKIs potentially inducing a chronic inflammatory response.

Recent research on the human microbiota highlights its importance in health. The microbiota plays a critical role in gut health, immune function, and metabolic processes, and its imbalances (dysbiosis) can contribute to a range of diseases. Factors such as diet, age, physical activity, and medication use can disrupt the microbiota. However, the relationship between gut microbiota and TKIs in CML patients remains unexplored.

The current study will evaluate by whether different CML gut microbiota genotypes influence TKI treatment responses, whether microbiota alterations cause inflammation or metabolic disorders, and whether microbiota, along with dysmetabolism and dysimmunity, contribute to variations in treatment efficacy and tolerance

Eligibility criteria: Inclusion Criteria:

* Age \> 18 years old
* Chronic Myeloid Leukemia Patients
* Any stage of the disease

Exclusioni Criteria:

none

Primary outcomes:
measure: genotypes of the intestinal microbiota and responses to treatment with TKI.
timeFrame: 4 years
Secondary outcomes:
Other outcomes:
Locations:
city: Torino
country: Italy
facility: AO Ordine Mauriziano di Torino
Study officials:
affiliation: Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
name: Carmen Fava
role: PRINCIPAL_INVESTIGATOR
References: