Circulating Tumor DNA in Peripheral T-cell Lymphomas (CIRCULATE)

Next-Generation Sequencing-based, Tumor- and Plasma-informed Droplet Digital PCR Assay for Detection of Circulating Tumor DNA in Peripheral T-cell Lymphomas

The aim of this study is to evaluate the feasibility of circulating tumor DNA (ctDNA) measurement in blood plasma for the applicability in prognostication, treatment evaluation and measurable residual disease (MRD) surveillance in a cohort of patients with newly diagnosed or relapsed/refractory peripheral T-cell lymphomas (PTCL).

Study Overview

• Status: Active, not recruiting
• Conditions: Peripheral T-cell Lymphoma; NK/T-Cell Lymphoma
• Intervention / Treatment: Diagnostic test: 18F-fludeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT); Diagnostic test: Tumor- and plasma-informed, next-generation sequencing (NGS)-based patient-specific droplet digital (dd)PCR assay

Detailed Description

In this observational prospective cohort study the investigators want to test the use of minimal-invasive liquid biopsies (blood plasma) for the detection of ctDNA in patients with newly diagnosed or relapsed/refractory PTCL. In each enrolled patient a diagnostic tumor-containing tissue biopsy as well as a baseline plasma sample will be subject to targeted next-generation sequencing (NGS) with the aim of identifying tumor-specific genetic alterations and clonal T-cell receptor rearrangements. This testing will be performed on biopsies that have been obtained as a part of standard-of-care diagnostic evaluation for PTCL and no further invasive biopsies will be performed.

Based on the NGS-analysis, a droplet digital polymerase chain reaction (ddPCR) assay will be designed for each patient. ddPCR will be used to detect ctDNA in plasma at diagnosis and later at defined time points during treatment and in the follow-up period.

At the same defined time points PET/CT scans will be performed for later comparative analysis. PTCL patients routinely have PET/CT scans performed before the start of treatment, mid-treatment, at the end of treatment and after hematopoietic stem cell transplant when applicable. PET/CT scans will be conducted every 6 months for the first 2 years of routine follow-up.

Active patient participation (i.e. blood sampling for ctDNA analysis and PET/CT scans) is expected to last up to 27 months from inclusion. Follow-up for survival analysis will be done for up to 5 years from inclusion.

The investigators hypothesize that the NGS-based tumor- and plasma-informed ddPCR assay applied in this study, will provide a highly sensitive and specific tool for prognostication, response evaluation and detection of relapse in patients with PTCL.

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

Contacts and Locations

Study Locations

• Denmark
  • Central Jutland
    • Aarhus, Central Jutland, Denmark, 8200
      • Department of Hematology, Aarhus University Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with peripheral T-cell lymphomas managed at tertiary care hospitals in Denmark.

Description

Inclusion Criteria:

• Patients with newly diagnosed or relapsed/refractory peripheral T-cell lymphoma.
• All primary systemic PTCL entities from the International Consensus Classification 2022.
• ≥18 years of age.
• Life expectancy of 3 months or longer.
• ECOG performance status 0-4 at study entry (PS4 only if lymphoma-induced).
• Measurable disease.
• Written informed consent.

Exclusion Criteria:

• T-cell prolymphocytic leukemia
• T-cell large granular lymphocytic leukemia
• Chronic lymphoproliferative disorder of NK cells
• Adult T-cell leukemia / lymphoma
• Aggressive NK-cell leukemia
• Primary cutaneous T-cell lymphoma such as Sézary syndrome and Mycosis fungoides.
• Primary cutaneous CD30 positive T-cell lymphoproliferative disorders.
• Lymphomatoid papulosis.
• Primary cutaneous anaplastic large cell lymphoma.
• Primary cutaneous small/medium CD4-positive T-cell lymphoproliferative disorder.
• Primary cutaneous gamma-delta T-cell lymphoma.
• Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder.
• Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma.
• History of active cancer during the past year, except basal cell carcinoma of the skin or stage 0 cervical carcinoma (in situ).
• Unwillingness or inability to comply with the study protocol.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ctDNA occurrence	Proportion of patients with one or more measurable genetic alterations detected in plasma ctDNA by a tumor-informed, NGS-based patient-specific droplet digital PCR assay at baseline, cycle 2 day 1, cycle 3 day 1, mid-treatment, end of treatment, 6 month, 12 month, 18 month and 24 month follow-up.	Up to 27 months
ctDNA quantification	Median ctDNA levels in plasma by a tumor- and plasma-informed, NGS-based patient-specific droplet digital PCR assay at baseline, cycle 2 day 1, cycle 3 day 1, mid-treatment, end of treatment, 6 month, 12 month, 18 month and 24 month follow-up.	Up to 27 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Time from date of diagnosis until the date of disease progression or relapse or death from any cause, whichever occurred first.	Up to 5 years
Overall survival	Time from date of diagnosis to the date of death from any cause or the date of last follow-up. Patients who are event-free at their last follow-up evaluation will be censored at that time point.	Up to 5 years
Radiographic assessment by PET/CT	Description of tumor staging, metabolic tumor volume and total lesion glycolysis by 18F-fludeoxyglucose positron emission tomography/computed tomography (PET/CT) before treatment. Therapeutic response evaluation based on the 2014 Lugano classification criteria at mid-treatment, end of treatment, 6 month, 12 month, 18 month and 24 month follow-up.	Up to 27 months
Comparison of molecular and radiographic response	Concordance between detection of ctDNA (MRD-positive or MRD-negative) and therapeutic response assessed by PET/CT at mid-treatment, end of treatment, 6 month, 12 month, 18 month and 24 month follow-up.	Up to 27 months
Spatial and temporal mutational homo- or heterogeneity	Characterization of the con- or discordance between the genetic profile in tumor and plasma ctDNA at diagnosis and at relapse.	Up to 27 months
Fragment pattern analysis	Description of fragment sizes of ctDNA by capillary electrophoresis at baseline, cycle 2 day 1, cycle 3 day 1, mid-treatment, end of treatment, 6 month, 12 month, 18 month and 24 month follow-up.	Up to 27 months

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital
• Investigators: Study Chair: Francesco A d'Amore, MD, DMSc, Aarhus University Hospital and Aarhus University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: April 8, 2024
• First Submitted That Met QC Criteria: April 8, 2024
• First Posted (Actual): April 12, 2024

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Liquid biopsy; cfDNA; ctDNA; Circulating Tumor DNA; Cell Free DNA; mutational profiling
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Hemic and Lymphatic Diseases; Lymphoma, T-Cell, Peripheral; Lymphoma, Extranodal NK-T-Cell; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Diagnostic Imaging; Radiography; Image Interpretation, Computer-Assisted; Radiographic Image Enhancement; Image Enhancement; Photography; Tomography, X-Ray; Tomography, X-Ray Computed
• Other Study ID Numbers: 1-10-72-134-23

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