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NCT Number: NCT06724536

Interaction Between Gut Microbiota and TKIs in Defining the Clinical Outcomes of Patients With CML

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusioni Criteria:

none

Treatment and study plan

non interventional study with the use of biological samples.

Other

Patients will undergo to the follow evaluations:

Gut microbiome on stool samples by NGS (16S rRNA gene amplicon sequencing); Markers of impaired intestinal permeability [diaminoxidase (DAO), serum zonulin], and markers of inflammation of the GI tract (fecal calprotectin); Plasma inflammatory indices, cytokines (by Luminex), markers of autoimmunity, and metabolic profile; Acquired and adaptive immunity by multiparametric flow cytometry on PB samples.

Primary outcomes

  1. genotypes of the intestinal microbiota and responses to treatment with TKI.

    Time frame: 4 years

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Carmen Fava

CONTACT

[email protected]

00390115082224

Valentina Bonuomo

CONTACT

00390115082224

Sponsors and collaborators

Lead sponsor

Carmen Fava

Other

Collaborators

  • Novartis
  • Pfizer

Registry information

Official study title

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

Acronym: MICROBIO-LMC

Important dates

Study start
2022
Primary completion
2026
Study completion
2026
First posted
Dec 9, 2024
Registry last updated
Dec 9, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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