Design of New Personalized Therapeutic Approaches for Diffuse Large B-cell Lymphoma

In Europe diffuse large B-cell lymphoma (DLBCL) is a rare disease whereas in Italy it is not. Approximately 40% of DLBCL patients has refractory disease or will relapse after initial response. In onco-hematology, a role for gut microbiota (GM) in mediating immune activation in response to chemotherapy, has been suggested. In this scenario, the Investigators hypothesized that GM could play an important role in DLBCL prognosis and response to treatment, establishing a connection between lifestyle and clinical response. The project is aimed to the study of the functional GM layout in association with specific patterns of treatment response in de novo DLBCL undergoing standard first line chemo-immunotherapy. Results may build the scientific basis to design new and personalized intervention strategies (both in treatment approach and in life-style recommendations), to enhance clinical response and reduction of disease refractoriness through modulation of the gut microbial ecosystem.

Study Overview

• Status: Active, not recruiting
• Conditions: Diffuse Large B Cell Lymphoma
• Intervention / Treatment: Other: Gut microbiota samples

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• Italy
  • Bologna, Italy, 40138
    • Institute Of Hematology "Seràgnoli"
  • FC
    • Meldola, FC, Italy
      • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients affected by diffuse large B-cell lymphoma (DLBCL) undergoing therapy with front-line R-CHOP (rituximab-cyclophosphamide, doxorubicin, vincristine, prednisone).

Description

Inclusion Criteria:

1. Age ≥18 years
2. Patients affected by histologically confirmed diffuse large B-cell lymphoma
3. Patients amenable for therapy with RCHOP (RCHOP is the standard first line therapy for DLBCL and it scheduled regardless of participation in present study).
4. Patients must provide written informed consent.

Exclusion Criteria:

1. Concomitant second malignancy, other than lymphoma.
2. Previous anti-lymphoma therapy.
3. Pregnancy or breastfeeding.
4. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GM dysbiosis assessment (bacterial DNA of gut microbiota in all patients)	dysbiosis index: the dysbiosis index relies on the calculation of the weighted ratio between health-promoting and disease-associated GM components; relative abundance of GM biomarkers of an eubiotic GM state: all GM dysbiotic states share a common feature, i.e. the depletion of strategic health-promoting GM components such as Faecalibacterium prausnitzii and Lachnospiraceae. Thus, a GM dysbiotic state is determined by the assessment of a reduction of the abundance of these GM biomarkers below the thresholds characteristic of an eubiotc GM state.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to therapy	Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. when the PET scan was positive before therapy, a post-treatment residual mass of any size is permitted as long as it is PET negative and all lymph nodes and nodal masses must have regressed on CT to normal size ( 1.5 cm in their greatest transverse diameter for nodes 1.5 cm before therapy).	2 years

Collaborators and Investigators

• Sponsor: University of Bologna
• Investigators: Principal Investigator: Pier Luigi L Zinzani, Professor, Institute of Hematology "L. e A. Seràgnoli", University of Bologna

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 2, 2019
• Primary Completion (ANTICIPATED): July 20, 2023
• Study Completion (ANTICIPATED): December 20, 2023

Study Registration Dates

• First Submitted: December 19, 2018
• First Submitted That Met QC Criteria: January 4, 2019
• First Posted (ACTUAL): January 9, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: first line; response; microbiota; RCHOP; disease control; therapy toxicity
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: Oncopassport; RF-2016-02363730 (OTHER_GRANT: Italian Ministry of Health)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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