Personalized Risk Stratification Model of Follicular Lymphoma Patients

Multilayer Model for Personalized Risk Stratification of Follicular Lymphoma Patients

The study aims at developping and validating an integrated clinico-molecular model for an accurate identification of FL patients who are progression free and progressed, respectively, at 24 months after treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Follicular Lymphoma

Detailed Description

Already existing and coded tumor biological material and health-related personal data will be retrospectively collected. FL diagnosis will be confirmed by central pathology review. Tumor somatic mutations, immunoglobulin gene rearrangement and mutation status will be analyzed by targeted deep next generation sequencing of tumor genomic DNA. Gene expression profiling will be performed by targeted RNA-Seq of biopsy-derived RNA.

An immunohistochemistry panel assessing both tumor phenotype and microenvironment cellular composition will be assessed by Tissue macroarray. FISH will be performed to characterize the most recurrent follicular lymphoma chromosomal translocations.

The adjusted association between exposure variables and progression free survival will be estimated by Cox regression. This approach will provide the covariates independently associated with progression free survival that will be utilized in the development of a hierarchical molecular model to predict progression free survival at 24 months. The hierarchical order of relevance in predicting 24 months progression free survival among covariates will be established by recursive partitioning analysis. Overall, this approach will allow the development of a multilayer dynamic model for anticipating progression within 24 months from treatment.

The model developed in the training set will be tested in the validation sets and the model performance (c-index and net reclassification improvement) in the validation set will be compared with that in the training set. The accuracy of the multilayer model in predicting progression free survival at 24 months will be compared against the FLIPI using c-index and net reclassification improvement.

• Study Type: Observational
• Enrollment (Actual): 370

Contacts and Locations

Study Locations

• Italy
  • Novara, Italy, 28100
    • Azienda Ospedaliera Universitaria Maggiore della Carita
  • RE
    • Reggio Emilia, RE, Italy, 42123
      • Arcispedale Santa Maria Nuova, AUSL IRCSS, Hematology Department
• Switzerland
  • Tessin
    • Bellinzona, Tessin, Switzerland, 6500
      • Institute of Oncology Research
    • Locarno, Tessin, Switzerland
      • Institute of Pathology

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: Probability Sample

Study Population

Follicular lymphoma patients

Description

Inclusion Criteria:

• Diagnosis of FL after January 1st, 2004 (chemoimmunotherapy era)
• Availability of tumor material collected before initiation of medical therapy
• Availability of the baseline and follow-up annotations

Exclusion Criteria:

• None.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Training cohort; Cohort of follicular lymphoma patients for the development of the multilayer risk stratification model
Validation cohort; Cohort of follicular lymphoma patients for the validation of the developed multilayer risk stratification model

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy of multilayer personalized stratification model	Assessment of multilayer personalized stratification model accuracy in the identification of patients who are progression free at 24 months after first line therapy plus the proportion of patients correctly identified as progressed within 24 months after first line therapy	24 months after first line treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Time elapsed from treatment start to progression (event), death (event) or last follow-up (censoring)	From treatment start to progression / death / last follow-up, up to 13 years of follow-up
Overall survival	Time elapsed from treatment start to death (event) or last follow-up (censoring)	From treatment start to death / last follow-up, up to 13 years of follow-up
Time to transformation	Time elapsed between treatment start and transformation (event), progression without transformation (censoring), death (censoring) or last follow-up (censoring)	From treatment start to transformation or progression without transformation or death or last follow-up, up to 13 years of follow-up

Collaborators and Investigators

• Sponsor: Oncology Institute of Southern Switzerland
• Collaborators: Azienda Ospedaliero Universitaria Maggiore della Carita; Arcispedale Santa Maria Nuova-IRCCS; Institute of Pathology, Locarno, Ticino, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Actual): October 31, 2021
• Study Completion (Anticipated): October 31, 2023

Study Registration Dates

• First Submitted: February 6, 2018
• First Submitted That Met QC Criteria: February 12, 2018
• First Posted (Actual): February 19, 2018

Study Record Updates

• Last Update Posted (Actual): April 3, 2023
• Last Update Submitted That Met QC Criteria: March 31, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Personalized risk assessment; Risk stratification model
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Follicular
• Other Study ID Numbers: IOSI-EMA-004

Drug and device information, study documents

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