Deciphering the Role of Circular RNAs in ALKpositive Anaplastic Large-cell Lymphoma (CIRComa)

Deciphering the Role of Circular RNAs in the Pathogenesis and Therapy Resistance of ALKpositive Anaplastic Large-cell Lymphoma

The objective of thE project is to determine, whether circRNAs could be used as circulating prognostic and/or predictive biomarkers of ALK+ ALCL resistance to treatment and whether they can be exploited as therapeutic targets.

Study Overview

• Status: Active, not recruiting
• Conditions: ALK-Positive Anaplastic Large Cell Lymphoma
• Intervention / Treatment: Biological: RNAseq

Detailed Description

Anaplastic large-cell lymphoma (ALCL) is an aggressive T-cell pediatric lymphoma. 85% of ALK+ ALCL cases harbor a fusion between the nucleophosmin (NPM) and anaplastic lymphoma kinase (ALK) genes, leading to a constitutively activated and oncogenic fusion protein. Most ALK+ ALCL cases initially respond well to the frontline chemotherapy, but 30% of patients relapse and are of poor prognosis. Understanding the origins of therapy resistance is of major importance to improve treatment and patient prognosis. Current research highlights deregulated expression of regulatory non-coding RNAs (ncRNAs) as an important factor in therapy resistance. To date, microRNAs and long noncoding RNAs have been linked to therapy resistance in ALK+ ALCL. Circular RNAs (circRNAs) are a class of highly stable noncoding RNAs that have recently come into the focus of researchers. circRNAs can control target gene expression by e.g. interacting with microRNAs or proteins. This project aims to elucidate their role in ALK+ ALCL biology including their impact on noncoding RNA networks and therapy resistance. This project will (1) identify a signature of circRNAs associated with therapy resistance in ALK+ ALCL, (2) analyze their effect on treatment response, (3) elucidate their mechanism of action, and (4) evaluate circRNA candidates as predictive and prognostic plasma biomarkers using liquid biopsies. The goal of the study is to characterize the role of candidate circRNAs in this well-defined cancer type, which can serve as a model for other ALK+ cancers. Project results will add to the current mechanistic understanding of ALK+ ALCL pathogenesis and the origins of therapy resistance, and could define new druggable targets and associated predictive biomarkers for high-risk disease. Establishing the blood-based alternative confirmation for the ALK+ ALCL diagnosis could also produce a less invasive predictive tool capable of longitudinal patient monitoring for early relapse detection.

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• France
  • Toulouse, France, 31500
    • IUCT-Oncopole University Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

patient at diagnosis of ALK+ ALCL, patient at the time of relapse for ALK+ ALCL, patient without ALK+ ALCL

Description

Inclusion Criteria:

• patient at diagnosis of ALK+ ALCL
• patient at the time of relapse for ALK+ ALCL
• patient without ALK+ ALCL

Exclusion Criteria:

-

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ALCL patient samples (serum); serum collected at diagnosis, during treatment and/or at relapse	Biological: RNAseq; there is no intervention done.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with relapse and circulating circRNA	RNAseq analysis	1 year after the end of treatment

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Laurence Lamant, University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Actual): June 1, 2023
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: June 23, 2023
• First Submitted That Met QC Criteria: July 3, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 3, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: cancer
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, T-Cell; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Anaplastic
• Other Study ID Numbers: RC31/22/0507; French Ministry of Health (Other Grant/Funding Number: PRT-K22-051)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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