Clinical trial NCT06712459: Integrated Molecular and Clinical Profiling of Transformed Splenic Marginal Zone Lymphoma
Official title: Integrated Molecular and Clinical Profiling of Transformed Splenic Marginal Zone Lymphoma
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Transformed Splenic Marginal Zone Lymphoma
Lead sponsor: International Extranodal Lymphoma Study Group (IELSG)
Sponsor class: OTHER
First posted: 2024-12-02
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Adult patients with transformed SMZL

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Prevalence of mutations, copy number abnormalities and structural variants at SMZL diagnosis and at HT
timeFrame: 30 months: from the end of samples collection to the end of study analysis
measure: Quantification and qualification of lesions acquired at the time of HT.
timeFrame: 30 months: from the end of samples collection to the end of study analysis
measure: Prevalence of clonal relationship between SMZL and HT
timeFrame: 30 months: from the end of samples collection to the end of study analysis
Secondary outcomes:
measure: Prevalence of HT molecular subtypes defined by genetic lesions
timeFrame: 30 months: from the end of samples collection to the end of study analysis
measure: Prevalence of Histological Transformation (HT) molecular subtypes defined by gene expression
timeFrame: 30 months: from the end of samples collection to the end of study analysis
measure: Prevalence of HT molecular subtypes defined by genetic methylation profile
timeFrame: 30 months: from the end of samples collection to the end of study analysis
measure: Prevalence of molecular features in relation with clinical, laboratory and radiological/Positron Emission Tomography (PET) features at SMZL diagnosis and at HT
timeFrame: 30 months: from the end of samples collection to the end of study analysis
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University
state: New York
city: Leuven
country: Belgium
facility: Universitz Hospitals Leuven
city: Paris
country: France
facility: Hôpital Saint Louis
city: Heidelberg
country: Germany
facility: University of Heidelberg
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Bellinzona
country: Switzerland
facility: Oncology Institute of Southern Switzerland
city: Bournemouth
country: United Kingdom
facility: University Hospitals Dorset
Study officials:
affiliation: Fondazione IRCCS Policlinico San Matteo
name: Luca Arcaini, MD
role: STUDY_CHAIR
affiliation: Oncology Institute of Southern Switzerland (IOSI) and Institute of Oncology Research (IOR)
name: Davide Rossi, MD
role: STUDY_CHAIR
References: