Diagnosis; Objective RespOnse; THErApy

NCT05036564 | Recruiting DMC

• 1 other identifier: DOROTHEA
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Thi is a prospective and low-intervention clinical trial. We propose to design a panel of "core" genetic alterations by sequencing Cerebral Spinal Fluid (CSF) DNA in patients with confirmed or suspicious Primary Central Neurvous System Lymphoma (PCNSL) with the aim to improve diagnostic sensitivity, response assessment and monitoring early CNS relapse in routine practice. Enrolled patients will receive conventional treatments according to well-established international guidelines, DNA assessments will not influence the treatment choices.

Conditions

Primary CNS Lymphoma

Keywords

PCNSL; ctDNA; CSF

Outcome Measures

Primary Outcomes (2)

• Association between recurrent genetic alterations and PCNSL diagnosis or relapse

  Frequency of various genetic mutations among enrolled patients at diagnosis or relapse

  3 years and 6 months

• Association between recurrent genetic alterations and residual enhanced and not-enhanced images at the MRI

  Frequency of various genetic mutations among enrolled patients during treatment

  3 years and 6 months

Study Arms (2)

Study population - PCNSL

EXPERIMENTAL

Patients (pts) with clinical and radiological suspicion of PCNSL or with confirmed diagnosis of PCNSL will be enrolled to the protocol. They will represent the "Study population"

Procedure: Lumbar puncture

Control

OTHER

1. Pts with suspicion of secondary CNS lymphoma, that includes subjects with DLBCL and involvement of the CNS at presentation in association with systemic disease, or subjects with systemic DLBCL and CNS relapse during or after primary therapy. 2. Pts with histological diagnosis of systemic DLBCL at high risk of CNS relapse according to Institutional guidelines and patients with histological diagnosis of systemic high grade B cell lymphoma, according to 2017 WHO classification; 3. pts affected by neurological disorders that are usually differential diagnosis of PCNSL (i.e. neurodegenerative and neuroinflammatory disorders, toxic or infective encephalitis, other primary CNS tumors).

Procedure: Lumbar puncture

Interventions

Lumbar puncture PROCEDURE

A lumbar puncture (spinal tap) is performed in patient lower back, in the lumbar region. During a lumbar puncture, a needle is inserted between two lumbar bones (vertebrae) to remove a sample of cerebrospinal fluid (CSF). This is the fluid that surrounds brain and spinal cord to protect them from injury. This procedure is usually performed at the time of diagnosis for disease staging and/or repeated in the course of the disease history, only if positive or for clinical reasons (i.e. suspicious of relapse progression). In this study sequential CSF and peripheral blood samples of study population will be collected also at different time points, with the aim to improve diagnostics sensitivity, response assessment and monitoring early CNS relapse.

Control; Study population - PCNSL

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Newly diagnosed PCNSL with available clinical and radiological data, CSF and histopathological brain biopsy material fresh and/or formalin fixed and paraffin embedded;
• No contraindications to stereotactic or open brain biopsy and lumbar puncture;
• No formal contraindications to intravenous chemo-immunotherapy or whole-brain irradiation;
• Given written informed consent prior to any study specific procedures, with the understanding that the patient has the right to withdraw from the study at any time, without any prejudice.

You may not qualify if:

• Patients with concomitant CNS and systemic involvement at presentation (potentially eligible as "control"; see below)
• Patients with CNS lymphoma other than DLBCL subtype
• Any other serious medical condition which could impair the ability of the patient to participate in the trial
• Pregnant and lactating female patients. Sexually active patients of childbearing potential must implement adequate contraceptive measures during study participation.
• Previous or concurrent malignancies at other sites diagnosed or relapsed within the last 3 years before PCNSL diagnosis. Patients with surgically cured in situ carcinomas and basal cell carcinoma of the skin are allowed.
• Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
• Age ≥18 years
• Newly diagnosed DLBCL with a high risk for relapse/progression in the CNS or High-grade B-cell (HGBC) lymphoma with available clinical and radiological data, CSF and diagnostic histopathological specimen. 3. Newly diagnosed and/or relapsed SCNSL with available clinical and radiological data, CSF and diagnostic histopathological specimen. 4. Newly diagnosed lymphoma confined to CNS other than DLBC subtype 5. Neoplastic and non-neoplastic neurological disorders (neurodegenerative and neuroinflammatory disorders, toxic or infective encephalitis, primary CNS tumors other than lymphomas (mainly gliomas)) with available clinical and radiological data, CSF samples and, where possible, histo-pathological brain biopsy material formalin fixed and paraffin embedded.
• \. No contraindications to stereotactic or open brain biopsy and lumbar puncture; 7. Given written informed consent prior to any study specific procedures, with the understanding that the patient has the right to withdraw from the study at any time, without any prejudice.
• Patients with extra-CNS lymphoma other than DLBC or HGBC subtypes, and not classified as high risk of CNS relapse;
• Any other serious medical condition which could impair the ability of the patient to participate in the trial;
• Pregnant and lactating female patients. Sexually active patients of childbearing potential must implement adequate contraceptive measures during study participation;
• Previous or concurrent malignancies at other sites diagnosed or relapsed within the last 3 years of follow-up. Patients with surgically cured in situ carcinomas and basal cell carcinoma of the skin are allowed;
• Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Sponsors & Collaborators

• IRCCS San Raffaele: lead
• Teresa Calimeri: collaborator
• Sara Steffanoni: collaborator

Study Sites (1)

IRCCS Ospedale San Raffaele

Milan, Italy/Lombardy, 20132, Italy

RECRUITING

MeSH Terms

Interventions

Spinal Puncture

Intervention Hierarchy (Ancestors)

Biopsy; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Andrés J.M. Ferreri, MD

  IRCCS Ospedale San Raffaele

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrés J.M. Ferreri, MD

CONTACT

02 2643 7649; ferreri.andres@hsr.it

Teresa Calimeri, MD/PhD

CONTACT

02 2643 7612; calimeri.teresa@hsr.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator; Lymphoma Unit, Head

Study Record Dates

• First Submitted: May 7, 2021
• First Posted: September 5, 2021
• Study Start: October 16, 2020
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): April 30, 2027
• Last Updated: May 31, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)