Diagnosis; Objective RespOnse; THErApy

Official title

Mutational Analysis in the Cerebrospinal Fluid to Improve Diagnostic Sensitivity, Response Definition and Precision Treatment in Primary Central Nervous System Lymphoma

Overview

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.

Interventions

• Procedure Lumbar puncture
  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

Primary outcome measures

• Association between recurrent genetic alterations and PCNSL diagnosis or relapse [Time frame: 3 years and 6 months]
• Association between recurrent genetic alterations and residual enhanced and not-enhanced images at the MRI [Time frame: 3 years and 6 months]

Eligibility criteria

Inclusion Criteria for study population:

• 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.

Exclusion Criteria for study population:

• 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.

Inclusion criteria for controls:

• 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.

6\. 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.

Exclusion criteria for controls:

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

Italy · 1 center

• IRCCS Ospedale San Raffaele — Milan

Identifiers

NCT: NCT05036564 · DOROTHEA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗