Trial Title:
LIBERTY: Liquid Biopsy to Diagnose and Monitor CNS Involvement in High-risk B Cell Non-Hodgkin Lymphoma
NCT ID:
NCT06090162
Condition:
Non-hodgkin Lymphoma, B Cell
Conditions: Official terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Conditions: Keywords:
High-risk B Cell Non-Hodgkin Lymphoma
ctDNA
experimental diagnostic test
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
This is a multicenter prospective diagnostic study to compare the performance of
experimental diagnostic test (ctDNA) versus conventional cytology (CC) and flow cytometry
(FC).
Primary purpose:
Diagnostic
Masking:
None (Open Label)
Intervention:
Intervention type:
Diagnostic Test
Intervention name:
ctDNA detection
Description:
ctDNA detection on CSF and blood
Arm group label:
experimental diagnostic test
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Kantonspital Aarau
Address:
City:
Aarau
Zip:
5001
Country:
Switzerland
Status:
Not yet recruiting
Contact:
Last name:
Marc Heizmann, MD
Phone:
+41 62 838 60 50
Email:
marc.heizmann@ksa.ch
Investigator:
Last name:
Marc Heizmann, MD
Email:
Principal Investigator
Facility:
Name:
Universitätsspital Basel
Address:
City:
Basel
Zip:
4056
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Benjamin Kasenda, MD
Phone:
+41 61 265 50 74
Email:
benjamin.kasenda@usb.ch
Investigator:
Last name:
Benjamin Kasenda, MD
Email:
Principal Investigator
Facility:
Name:
Istituto Oncologico della Svizzera Italiana (IOSI)
Address:
City:
Bellinzona
Zip:
6500
Country:
Switzerland
Status:
Not yet recruiting
Contact:
Last name:
Maria Pirosa, MD
Phone:
+41 91 811 94 79
Email:
maria.pirosa@eoc.ch
Investigator:
Last name:
Maria Pirosa, MD
Email:
Principal Investigator
Facility:
Name:
Inselspital Bern - Universitätsklinik für Medizinische Onkologie
Address:
City:
Bern
Zip:
3010
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Urban Novak, MD
Phone:
+41 31 632 22 43
Email:
urban.novak@insel.ch
Investigator:
Last name:
Urban Novak, MD
Email:
Principal Investigator
Facility:
Name:
Kantonsspital Graubünden
Address:
City:
Chur
Zip:
7000
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Ulrich Mey, Prof
Phone:
41 81 256 71 70
Email:
ulrich.mey@ksgr.ch
Investigator:
Last name:
Ulrich Mey, Prof
Email:
Principal Investigator
Facility:
Name:
Hôpital Fribourgeois - Hôpital Cantonal
Address:
City:
Fribourg
Zip:
1708
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Gaëlle Rhyner Agocs, MD
Phone:
+41 26 306 00 00
Email:
gaelle.rhyner@h-fr.ch
Investigator:
Last name:
Gaëlle Rhyner Agocs, MD
Email:
Principal Investigator
Facility:
Name:
Hopitaux Universitaire de Genève (HUG)
Address:
City:
Geneva
Zip:
1205
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Noémie Lang, MD
Phone:
+41 22 372 33 11
Email:
noemie.lang@hcuge.ch
Investigator:
Last name:
Noémie Lang, MD
Email:
Principal Investigator
Facility:
Name:
CHUV - Départment d'oncologie
Address:
City:
Lausanne
Zip:
1011
Country:
Switzerland
Status:
Not yet recruiting
Contact:
Last name:
Amandine Segot, MD
Phone:
+41 78 212 58 64
Email:
amandine.segot@chuv.ch
Investigator:
Last name:
Amandine Segot, MD
Email:
Principal Investigator
Facility:
Name:
Kantonsspital Baselland
Address:
City:
Liestal
Zip:
4410
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Michèle Voegeli, MD
Phone:
+41 61 925 27 10
Email:
michele.voegeli@ksbl.ch
Investigator:
Last name:
Michèle Voegeli, MD
Email:
Principal Investigator
Facility:
Name:
Hôpital du Valais, Hôpital de Sion
Address:
City:
Sion
Zip:
1951
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Grégoire Berthod, MD
Phone:
+41 27 603 87 71
Email:
gregoire.berthod@hopitalvs.ch
Investigator:
Last name:
Grégoire Berthod, MD
Email:
Principal Investigator
Facility:
Name:
Kantonsspital St. Gallen
Address:
City:
St. Gallen
Zip:
9007
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Felicitas Hitz, MD
Phone:
+41 71 494 11 11
Email:
felicitas.hitz@kssg.ch
Investigator:
Last name:
Felicitas Hitz, MD
Email:
Principal Investigator
Facility:
Name:
Klinik für Hämatologie und Onkologie Hirslanden Zürich
Address:
City:
Zurich
Zip:
8032
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Christoph Renner, Prof
Phone:
+41 43 387 37 80
Email:
christoph.renner@kho.ch
Investigator:
Last name:
Christoph Renner, Prof
Email:
Principal Investigator
Facility:
Name:
Stadtspital Triemli Zürich
Address:
City:
Zürich
Zip:
8063
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Adrian Schmidt, MD
Phone:
+41 44 416 35 05
Email:
adrian.schmidt@stadtspital.ch
Investigator:
Last name:
Adrian Schmidt, MD
Email:
Principal Investigator
Start date:
March 12, 2024
Completion date:
December 2026
Lead sponsor:
Agency:
Swiss Group for Clinical Cancer Research
Agency class:
Other
Source:
Swiss Group for Clinical Cancer Research
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06090162
