Integrated Molecular and Clinical Profiling of Transformed Splenic Marginal Zone Lymphoma

Histological transformation in Splenic Marginal Zone Lymphoma (t-SMZL) represents an unmet clinical and biological need, invariably associated with poor prognosis and reduced overall survival. At the present time, there are no recommended treatments intended specifically to t-SMZL and little is known about t-SMZL genetic complexity. The aim of this study is to provide information that will help clinicians to better understand the complexity of the disease. The information gained from this study will also lead to more specific and effective treatment for patients with t-SMZL.

Study Overview

• Status: Recruiting
• Conditions: Transformed Splenic Marginal Zone Lymphoma

Detailed Description

Already existing and coded tumor biological material and health-related patient data will be retrospectively collected from institutional biobanks and patients' charts or electronic medical records upon receipt of ethical approval. Each patient enrolled in the study will be assigned a unique identification numerical code upon registration in the study. The unique identification code will be used to record health-related data and to label biological samples. Health-related data will be collected by electronic case report form (e-CRF) system. Data quality will be insured by query generation.

Annotated baseline features will include: date of diagnosis, date and tissue type of histological sample collected at diagnosis (spleen and/or bone marrow), age, gender, Eastern Cooperative Oncology Group - Performing Status (ECOG-PS), Ann Arbor stage, Lactate Dehydrogenase (LDH), number and location of extranodal sites, bone marrow involvement and percentage, peripheral blood involvement, bulky disease (>7 cm), number of nodal sites, B symptoms, hemoglobin, platelets, lymphocytes, beta-2-microglobulin, albumin, Hepatitis C Virus (HCV) infection, serum paraprotein and type.

Annotated follow-up features will include: the date of progression to a disease requiring treatment, type of first line treatment, date of start of the first line treatment, date of progression after first line treatment, date of the second line treatment, type of second line treatment.

Annotated transformation features will include: date of transformation, date and type of histological sample collected at transformation (spleen and/or bone marrow and/or lymph node and/or other site), histological transformation type and relative molecular data (if available), ECOG-PS, Ann Arbor stage, LDH, number and location of extranodal sites, bone marrow involvement and percentage, peripheral blood involvement, bulky disease (>7 cm), number of nodal sites, B symptoms, hemoglobin, platelets, lymphocytes, beta-2-microglobulin, albumin, serum paraprotein, and type.

Survival features will include the date of death, cause of death, date of last follow-up.

Mutation analysis, immunoglobulin gene rearrangement analysis, copy number aberration analysis, structural variant analysis, and DNA methylation profile will be performed by Next Generation Sequencing (NGS) of genomic DNA extracted from the biological sample available for the analysis. Gene expression will be assessed by NGS of RNA extracted from from the biological sample available for the analysis.

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

Contacts and Locations

• Study Contact: Name: Davide Rossi, MD; Phone Number: +41 91 811 8540; Email: davide.rossi@eoc.ch
• Study Contact Backup: Name: IELSG Study Coordination Office; Phone Number: +41 58 666 7321; Email: ielsg@ior.usi.ch

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Not yet recruiting
    • Universitz Hospitals Leuven
    • Contact: Thomas Tousseyn, MD; Email: thomas.tousseyn@kuleuven.be
    • Principal Investigator: Thomas Tousseyn, MD
• France
  • Paris, France, 75475
    • Recruiting
    • Hopital Saint Louis
    • Principal Investigator: Catherine Thieblemont, MD
    • Contact: Catherine Thieblemont, MD; Email: catherine.thieblemont@aphp.fr
• Italy
  • Pavia, Italy, 27100
    • Recruiting
    • Fondazione IRCCS Policlinico San Matteo
    • Contact: Luca Arcaini, MD; Email: luca.arcaini@unipv.it
    • Principal Investigator: Luca Arcaini, MD
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic De Barcelona
    • Contact: ARMANDO LÓPEZ GUILLERMO, MD
    • Contact: Email: alopezg@clinic.cat
    • Principal Investigator: Armando Hospital Clínic de Barcelona, MD
• Switzerland
  • Bellinzona, Switzerland, 6500
    • Not yet recruiting
    • Oncology Institute of Southern Switzerland
    • Principal Investigator: Maria Cristina Pirosa, MD
    • Contact: Maria Cristina Pirosa, MD; Email: maria.pirosa@eoc.ch
• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • Not yet recruiting
    • University Hospitals Dorset
    • Contact: Renata Walewska, MD; Email: Renata.Walewska@uhd.nhs.uk
    • Principal Investigator: Renata Walewska, MD
• United States
  • New York
    • New York, New York, United States, 10032
      • Not yet recruiting
      • Columbia University
      • Contact: Govind Bhagat, MD; Email: gb96@cumc.columbia.edu
      • Principal Investigator: Govind Bhagat, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Adult patients with transformed SMZL

Description

Inclusion Criteria:

1. Adults aged 18 years or older, regardless of the gender;
2. Diagnosis of HT of SMZL (both at baseline, co-occurring with diagnosis of SMZL, or during the natural history of the disease);
3. Availability of diagnostic tumor material (either frozen or FFPE) from spleen, lymph node, extra nodal site, peripheral blood or bone marrow collected at the time of histological transformation. Tumor material (either frozen or FFPE), from spleen, peripheral blood or bone marrow, collected at the time of SMZL diagnosis will be also collected, if available;
4. Availability of the baseline and follow-up annotations.

Exclusion Criteria:

• None

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Prevalence of mutations, copy number abnormalities and structural variants at SMZL diagnosis and at HT	30 months: from the end of samples collection to the end of study analysis
Quantification and qualification of lesions acquired at the time of HT.	30 months: from the end of samples collection to the end of study analysis
Prevalence of clonal relationship between SMZL and HT	30 months: from the end of samples collection to the end of study analysis

Secondary Outcome Measures

Outcome Measure	Time Frame
Prevalence of HT molecular subtypes defined by genetic lesions	30 months: from the end of samples collection to the end of study analysis
Prevalence of Histological Transformation (HT) molecular subtypes defined by gene expression	30 months: from the end of samples collection to the end of study analysis
Prevalence of HT molecular subtypes defined by genetic methylation profile	30 months: from the end of samples collection to the end of study analysis
Prevalence of molecular features in relation with clinical, laboratory and radiological/Positron Emission Tomography (PET) features at SMZL diagnosis and at HT	30 months: from the end of samples collection to the end of study analysis

Collaborators and Investigators

• Sponsor: International Extranodal Lymphoma Study Group (IELSG)
• Investigators: Study Chair: Luca Arcaini, MD, Fondazione IRCCS Policlinico San Matteo; Study Chair: Davide Rossi, MD, Oncology Institute of Southern Switzerland (IOSI) and Institute of Oncology Research (IOR)

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2025
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: November 26, 2024
• First Submitted That Met QC Criteria: November 26, 2024
• First Posted (Actual): December 2, 2024

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, B-Cell, Marginal Zone
• Other Study ID Numbers: IELSG54

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No