Clinical trial NCT06362148: Circulating Tumor DNA in Peripheral T-cell Lymphomas
Official title: Next-Generation Sequencing-based, Tumor- and Plasma-informed Droplet Digital PCR Assay for Detection of Circulating Tumor DNA in Peripheral T-cell Lymphomas
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Peripheral T-cell Lymphoma
NK/T-Cell Lymphoma
Keywords: Liquid biopsy
Circulating Tumor DNA
ctDNA
Cell Free DNA
cfDNA
mutational profiling
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
First posted: 2024-04-12
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with peripheral T-cell lymphomas managed at tertiary care hospitals in Denmark.

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: ctDNA occurrence
timeFrame: Up to 27 months
measure: ctDNA quantification
timeFrame: Up to 27 months
Secondary outcomes:
measure: Progression free survival
timeFrame: Up to 5 years
measure: Overall survival
timeFrame: Up to 5 years
measure: Radiographic assessment by PET/CT
timeFrame: Up to 27 months
measure: Comparison of molecular and radiographic response
timeFrame: Up to 27 months
measure: Spatial and temporal mutational homo- or heterogeneity
timeFrame: Up to 27 months
measure: Fragment pattern analysis
timeFrame: Up to 27 months
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Department of Hematology, Aarhus University Hospital
state: Central Denmark Region
Study officials:
affiliation: Aarhus University Hospital and Aarhus University
name: Francesco A d'Amore, MD, DMSc
role: STUDY_CHAIR
affiliation: Aarhus University Hospital and Aarhus University
name: Patrick R Noerhave, MD
role: PRINCIPAL_INVESTIGATOR
References: