Interaction Between Gut Microbiota and TKIs in Defining the Clinical Outcomes of Patients With CML (MICROBIO-LMC)

Interaction Between Gut Microbiota and Tyrosine Kinase Inhibitors in Defining the Clinical Outcomes of Patients With Chronic Myeloid Leukemia

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.

Study Overview

• Status: Recruiting
• Conditions: Leukemia,Myeloid, Chronic
• Intervention / Treatment: Other: non interventional study with the use of biological samples.

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

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Carmen Fava; Phone Number: 00390115082224; Email: carmen.fava@unito.it
• Study Contact Backup: Name: Valentina Bonuomo; Phone Number: 00390115082224

Study Locations

• Italy
  • Torino, Italy, 10128
    • Recruiting
    • AO Ordine Mauriziano di Torino
    • Contact: Carmen Fava; Phone Number: 00390115082224; Email: carmen.fava@unito.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

Inclusion Criteria:

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

Exclusioni Criteria:

none

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
genotypes of the intestinal microbiota and responses to treatment with TKI.	The primary objective is to assess the association between genotypes of the intestinal microbiota (in eubiosis or dysbiosis) of patients with CML and responses (efficacy and tolerability in the short and long term) to treatment with TKI.	4 years

Collaborators and Investigators

• Sponsor: Carmen Fava
• Collaborators: Novartis; Pfizer
• Investigators: Principal Investigator: Carmen Fava, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: December 4, 2024
• First Submitted That Met QC Criteria: December 4, 2024
• First Posted (Estimated): December 9, 2024

Study Record Updates

• Last Update Posted (Estimated): December 9, 2024
• Last Update Submitted That Met QC Criteria: December 4, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: microbiota; gut; chronic myeloid leukemia; tyrosine kinase inhibitors
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: MICROBIO-LMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No