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

NCT06090162 | Active Not Recruiting DMC

• 1 other identifier: SAKK 38/23
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 14

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.

Conditions

Non-hodgkin Lymphoma, B Cell

Keywords

High-risk B Cell Non-Hodgkin Lymphoma; ctDNA; experimental diagnostic test

Outcome Measures

Primary Outcomes (1)

• Sensitivity

  Sensitivity of liquid biopsy (ctDNA) measured within CSF in its performance to detect CNS involvement in newly diagnosed high-risk B-NHL in comparison to standard conventional diagnostic approaches (CC / FC). For the evaluation of the primary endpoint, only patients with confirmed CNS involvement at baseline (real positives) will be analyzed. CNS involvement at baseline is defined as having at least one of the following conditions: * Positive brain or spine MRI * Neurological symptoms of lymphoma manifestations (including ophthalmic symptoms) * Histologically confirmed CNS involvement

  at baseline

Secondary Outcomes (8)

• Specificity

  at baseline

• Time to lymphoma manifestation in the CNS

  from the date of registration until the date of assessment of neurological symptoms or death due to lymphoma, assessed up to 1 year after registration

• Progression-free survival (PFS)

  from the date of registration until the date of progression or relapse as per Lugano and / or IPCG criteria, or death whatever occurs first, assessed up to 1 year after registration

• Event-free survival (EFS)

  from the date of registration until the date of progression or relapse as per Lugano and / or IPCG criteria, treatment stop without achieving a complete response or death whatever occurs first, assessed up to 1 year after registration

• Overall survival (OS)

  from the date of registration until the date of death, assessed up to 1 year after registration

Study Arms (1)

experimental diagnostic test

EXPERIMENTAL

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

Diagnostic Test: ctDNA detection

Interventions

ctDNA detection DIAGNOSTIC_TEST

ctDNA detection on CSF and blood

experimental diagnostic test

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (14)

Kantonspital Aarau

Aarau, 5001, Switzerland

Location

Universitätsspital Basel

Basel, 4056, Switzerland

Location

Istituto Oncologico della Svizzera Italiana (IOSI)

Bellinzona, 6500, Switzerland

Location

Inselspital Bern - Universitätsklinik für Medizinische Onkologie

Bern, 3010, Switzerland

Location

Kantonsspital Graubünden

Chur, 7000, Switzerland

Location

Hôpital Fribourgeois - Hôpital Cantonal

Fribourg, 1708, Switzerland

Location

Hopitaux Universitaire de Genève (HUG)

Geneva, 1205, Switzerland

Location

CHUV - Départment d'oncologie

Lausanne, 1011, Switzerland

Location

Kantonsspital Baselland

Liestal, 4410, Switzerland

Location

Kantonsspital Münsterlingen

Münsterlingen, 8596, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Hôpital du Valais, Hôpital de Sion

Sion, 1951, Switzerland

Location

Klinik für Hämatologie und Onkologie Hirslanden Zürich

Zurich, 8032, Switzerland

Location

Stadtspital Triemli Zürich

Zurich, 8063, Switzerland

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Noémie Lang, MD

  Hôpitaux Universitaires Genève

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicenter prospective diagnostic study to compare the performance of experimental diagnostic test (ctDNA) versus conventional cytology (CC) and flow cytometry (FC).

Study Record Dates

• First Submitted: October 12, 2023
• First Posted: October 19, 2023
• Study Start: March 12, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-03

Locations

CH (14)