Correlation Between Gut Microbiota and Clinical Response to CAR-T Treatment for Hematological Malignancies

Study Overview
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Brief Summary
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The purpose of this prospective and observational study is to evaluate the correlation between gut microbiota and clinical response to CAR-T treatment for hematological malignancies

Detailed Description
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Chimeric antigen receptor T-cell (CAR-T) therapy has shown impressive efficacy in hematological malignancies. However, response rates and associated immune-related adverse effects widely vary among patients. And no biomarkers have been identified to predict the efficacy and associated toxicities after CAR-T therapy in patients. Several preclinical experiments and clinical studies have shown that gut microbiota was associated with the efficacy of T cell-driven cancer immunotherapies and their toxicities. In hematologic malignancies, gut microbiota was associated with the development of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the potential correlation between gut microbiota and the effificacy and toxicity of CAR-T therapy is unclear. Therefore, in this study, we aim to evaluate the correlation between gut microbiota and clinical response to CAR-T treatment for hematological malignancies.

Official Title
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A Prospective and Observational Clinical Study of the Correlation Between Gut Microbiota and Clinical Response to CAR-T Treatment for Hematological Malignancies

Conditions
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Hematological Malignancies, Chimeric Antigen Receptor T-cell Therapy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 16-65 years. Hematologic malignancies intended for CAR-T therapy. Expected survival time ≥ 3 months (according to investigator's judgement). Left ventricular ejection fractions ≥ 55% by echocardiography. ALT / AST <3 times of normal amounts. Creatinine<2.0mg/dl. PT and APPT <2 times of normal amounts. Karnofsky performance status ≥ 60. The ECOG score ≤2 points. Exclusion Criteria: Pregnant (or lactating) women; Uncontrolled active infection； Active infection of hepatitis B virus or hepatitis C virus； Human immunodeficiency virus (HIV) positive； Patients with a history of myocardial infarction or severe arrhythmia within six months or those with class III or IV cardiac function according to the New York classification； Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 65 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| gut microbiota | diversity and composition of the gut microbiota | From pre-lymphodepletion regimen to day 28 after CAR-T cells infusion | 
| efficacy of CAR-T therapy | CR，PR and NR | six months | 
| toxicity of CAR-T therapy | Adverse events are evaluated with CTCAE V5.0 | six months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gut microbiota, CAR-T