LIBERTY: Liquid Biopsy to Diagnose and Monitor CNS Involvement in High-risk B Cell Non-Hodgkin Lymphoma

NCT ID: NCT06090162

Last Updated: 2025-10-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-12
• Study Completion Date: 2026-12-31

Brief Summary

Prevention and treatment of CNS relapse remains a great unmet clinical need in the management of aggressive B-NHL. Hence, investigating novel diagnostic tests is of paramount importance to improve risk-stratification of lymphoma patients at diagnosis, as is the evaluation of novel therapeutic approaches that may prevent and / or treat CNS recurrence. Based on the highlighted evidence, the investigators hypothesize that ctDNA detected within the CSF could potentially improve the detection rate of CNS involvement and consequently improve patients' stratification and better discriminate those in need of consolidative CNS prophylaxis on a molecular basis. Similarly, the investigators postulate that CSF ctDNA could be used as a monitoring tool to assess treatment response and guide therapeutic management.

Detailed Description

Non-Hodgkin B-cell lymphoma (B-NHL) are cancers that arise from a subtype of white blood cells (lymphocyte) and typically involve the lymphatic system; they represent 4% of all cancers [SEER database, access 2022]. Despite booming novel antineoplastic agent development, a significant number of aggressive B-NHL patients continue to succumb to their disease, experiencing rapidly progressive disease or early relapse. Central nervous system or CNS (brain, spinal cord and cerebrospinal fluid (CSF)) involvement in aggressive B-NHL is a rare (2-5%) but it is a devastating event, with a life expectancy ranging between 2 and 5 months [PMID: 30125215]. Circulating tumor DNA (ctDNA) represents fragmented DNA that originates from tumors cells, carrying specific cancer-associated mutations that can be detected in the blood or other fluids subsumed under "liquid biopsies".

The role of ctDNA gained momentum with the advent of high throughput sequencing technologies, becoming increasingly relevant for clinical practice. In lymphoma, detecting and monitoring ctDNA has been shown to be feasible and of high prognostic relevance regarding response and relapse. As such, ctDNA is emerging as a promising biomarker that can provide valuable diagnostic and prognostic information [PMID: 30125215, PMID: 29449275]. Identification of patients suffering from aggressive B-NHL at high risk of CNS relapse remains extremely challenging and currently mainly relies on a clinical score (CNS-IPI) [PMID: 27382100]. The detection of asymptomatic CNS is limited to conventional techniques and is not standardized [PMID: 22927246]. In patients with biopsy-proven CNS lymphoma, ctDNA can be detected in CSF (CSF ctDNA) in approximately 95% of cases. Furthermore, CSF ctDNA is predictive of CNS relapse in a small series of neurologically asymptomatic patients with aggressive B-NHL [PMID: 36542815, PMID: 32079701, PMID: 34551072]. Prevention and treatment of CNS involvement remains a great unmet clinical need. The discovery of novel and robust biomarkers is of paramount importance for early detection and risk-adapted therapeutic strategies for CNS involvement. The investigators hypothesize that CSF ctDNA is superior to current standard diagnostic procedures (e.g., flowcytometry or cytology) to detect CNS involvement in high-risk patients.

Furthermore, in patients with positive CSF ctDNA, the investigators also postulate that the concept of monitoring minimal residual disease (MRD, small amount of ctDNA that persists in patients that have no signs of active disease on standard imaging techniques) will provide additional information on patient prognosis.

This is a multicenter prospective diagnostic study to compare the performance of experimental diagnostic test (ctDNA) versus conventional cytology (CC) and flow cytometry (FC). Each high-risk B-NHL participant will proceed through standard work-up to evaluate potential CNS involvement including a neurological physical examination, a brain MRI and a diagnostic lumbar puncture. Each participant's CSF will be assessed by the two diagnostic tests (CSF ctDNA and conventional test (CC/FC)); the gold standard being proven CNS lymphoma involvement.

Conditions

Non-hodgkin Lymphoma, B Cell

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

experimental diagnostic test

Lumbar punction at diagnosis. CSF and blood samples will be assessed by the two diagnostic tests (CSF ctDNA and conventional test (CC/FC))

Group Type: EXPERIMENTAL

ctDNA detection

Intervention Type: DIAGNOSTIC_TEST

ctDNA detection on CSF and blood

Interventions

ctDNA detection

ctDNA detection on CSF and blood

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Informed consent as documented by signature before registration and prior to any trial specific procedures, according to Swiss law and ICH E6 regulations Swiss law and ICH GCP E6(R2) regulations before registration.
• Histologically and/or cytologically confirmed newly diagnosed lymphomas including the following:
• Diffuse large B-cell lymphoma (DLBCL) with at least one of the following characteristics:

• CNS IPI > 4
• Non-GC/ABC subtype with IPI > 3
• Testicular involvement
• Breast involvement
• Kidney involvement
• Adrenal involvement
• Paranasal sinus / orbit involvement
• Involvement of ≥ 3 extranodal sites
• HIV-positive
• Radiological or histological CNS involvement
• High-grade B-cell lymphoma with MYC translocation with BCL2 and / or BCL6 (HGBL)
• Burkitt lymphoma
• Mantle cell lymphoma (blastoid variant or Ki67 >30% or TP53 mutated)
• Primary CNS lymphoma

Note:

• Aggressive transformation from indolent lymphomas (pretreated or not) are allowed
• Patients enrolled in other clinical trials may be included

• Patients must be willing to undergo a lumbar puncture at screening
• Age ≥ 18 years

Exclusion Criteria

• Subtypes of Non-Hodgkin lymphoma (NHL) not fulfilling above mentioned criteria (e.g., indolent lymphoma, T-cell lymphoma)
• Relapsing B-NHL
• Low/intermediate-risk DLBCL (CNS-IPI < 4) AND no CNS involvement on imaging
• Any prior lymphoma-directed therapy before registration, with the exception of a maximum of 48 hours steroids prior to lumbar puncture procedure and therapies received for indolent lymphomas prior to transformation
• Any active advanced or metastatic cancer
• Any clinical contraindication to lumbar puncture procedure as per local guidelines
• Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned diagnostic procedure.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Noémie Lang, MD

Role: STUDY_CHAIR

Hôpitaux Universitaires Genève

Locations

Kantonspital Aarau

Aarau, , Switzerland

Site Status: NOT_YET_RECRUITING

Universitätsspital Basel

Basel, , Switzerland

Site Status: RECRUITING

Istituto Oncologico della Svizzera Italiana (IOSI)

Bellinzona, , Switzerland

Site Status: WITHDRAWN

Inselspital Bern - Universitätsklinik für Medizinische Onkologie

Bern, , Switzerland

Site Status: RECRUITING

Kantonsspital Graubünden

Chur, , Switzerland

Site Status: RECRUITING

Hôpital Fribourgeois - Hôpital Cantonal

Fribourg, , Switzerland

Site Status: RECRUITING

Hopitaux Universitaire de Genève (HUG)

Geneva, , Switzerland

Site Status: RECRUITING

CHUV - Départment d'oncologie

Lausanne, , Switzerland

Site Status: TERMINATED

Kantonsspital Baselland

Liestal, , Switzerland

Site Status: RECRUITING

Kantonsspital Münsterlingen

Münsterlingen, , Switzerland

Site Status: RECRUITING

Kantonsspital St. Gallen

Sankt Gallen, , Switzerland

Site Status: RECRUITING

Hôpital du Valais, Hôpital de Sion

Sion, , Switzerland

Site Status: RECRUITING

Klinik für Hämatologie und Onkologie Hirslanden Zürich

Zurich, , Switzerland

Site Status: WITHDRAWN

Stadtspital Triemli Zürich

Zurich, , Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Sabrina Chiquet

Role: CONTACT

trials@swisscancerinstitute.ch

+41 31 389 91 91

Noémie Lang, MD

Role: CONTACT

noemie.lang@hcuge.ch

+41 022 372 33 11

Facility Contacts

Marc Heizmann, MD

Role: primary

marc.heizmann@ksa.ch

+41 62 838 60 50

Benjamin Kasenda, MD

Role: primary

benjamin.kasenda@usb.ch

+41 61 265 50 74

Urban Novak, MD

Role: primary

urban.novak@insel.ch

+41 31 632 22 43

Ulrich Mey, Prof

Role: primary

ulrich.mey@ksgr.ch

41 81 256 71 70

Gaëlle Rhyner Agocs, MD

Role: primary

gaelle.rhyner@h-fr.ch

+41 26 306 00 00

Noémie Lang, MD

Role: primary

noemie.lang@hcuge.ch

+41 22 372 33 11

Michèle Voegeli, MD

Role: primary

michele.voegeli@ksbl.ch

+41 61 925 27 10

Felicitas Hitz, Prof

Role: primary

Felicitas.Hitz@stgag.ch

+41 58 144 55 32

Felicitas Hitz, MD

Role: primary

felicitas.hitz@kssg.ch

+41 71 494 11 11

Grégoire Berthod, MD

Role: primary

gregoire.berthod@hopitalvs.ch

+41 27 603 87 71

Adrian Schmidt, MD

Role: primary

adrian.schmidt@stadtspital.ch

+41 44 416 35 05

Other Identifiers

SAKK 38/23

Identifier Type: -

Identifier Source: org_study_id