NK/T-Cell Lymphoma, Peripheral T-cell Lymphoma
Conditions
Keywords
Liquid biopsy, Circulating Tumor DNA, ctDNA, Cell Free DNA, cfDNA, mutational profiling
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.
Interventions
DIAGNOSTIC_TESTTumor- and plasma-informed, next-generation sequencing (NGS)-based patient-specific droplet digital (dd)PCR assay
Blood sampling for circulating tumor DNA analysis at baseline, cycle 2 day 1, cycle 3 day 1, mid-treatment, end of induction/end of treatment, 100 day follow-up, 6 month, 12 month, 18 month and 24 month follow-up. Blood sampling will also be done in case of relapsing/refractory disease at any point prior to the abovementioned time points.
DIAGNOSTIC_TEST18F-fludeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT)
FDG-PET/CT performed at baseline, mid-treatment, end of induction/end of treatment and 6 month, 12 month, 18 month and 24 month follow-up.
Sponsors
University of Aarhus
Aarhus University Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ctDNA occurrence | Up to 27 months | 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. |
| ctDNA quantification | Up to 27 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | Up to 5 years | Time from date of diagnosis until the date of disease progression or relapse or death from any cause, whichever occurred first. |
| Overall survival | Up to 5 years | 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. |
| Radiographic assessment by PET/CT | Up to 27 months | 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. |
| Comparison of molecular and radiographic response | Up to 27 months | 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. |
| Spatial and temporal mutational homo- or heterogeneity | Up to 27 months | Characterization of the con- or discordance between the genetic profile in tumor and plasma ctDNA at diagnosis and at relapse. |
| Fragment pattern analysis | Up to 27 months | 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. |
Countries
Denmark
Contacts
STUDY_CHAIRFrancesco A d'Amore, MD, DMSc
Aarhus University Hospital and Aarhus University
Outcome results
None listed