Circulating Tumor DNA in Peripheral T-cell Lymphomas

Peripheral T-cell Lymphoma Clinical Trial

— CIRCULATE  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06362148
• Other study ID #: 1-10-72-134-23
• Status: Recruiting
• Start date: March 1, 2024
• Est. completion date: December 2030

Study information

• Verified date: March 2024
• Source: University of Aarhus
• Contact: Patrick R Noerhave, MD
• Phone: +4551543715
• Email: panoer[@]rm.dk
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2030
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• NK/T-Cell Lymphoma
• Peripheral T-cell Lymphoma

Intervention

Diagnostic Test:
• Tumor- 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.
• 18F-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.

Locations

Country	Name	City	State
Denmark	Department of Hematology, Aarhus University Hospital	Aarhus	Central Denmark Region

Sponsors (2)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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