[18F]-Fludarabine PET/MRI in Primary Central Nervous System Lymphoma

Primary Central Nervous System Lymphoma Clinical Trial

— FLUDALOC  

Official title:

[18F]-Fludarabine PET/MR Imaging for the Assessment of Newly-diagnosed Primary Central Nervous System (CNS) Lymphoma : a Pilot PET-MRI Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05390814
• Other study ID #: P160407
• Secondary ID: 2021-005193-26
• Status: Recruiting
• Phase: Phase 1
• Start date: December 18, 2023
• Est. completion date: June 15, 2025

Study information

• Verified date: June 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Aurélie KAS, Pr
• Phone: 01 42 17 62 81
• Email: aurelie.kas[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary central nervous system (CNS) lymphomas represent 5% of primary brain tumors. More than 90% of them are diffuse large B-cell lymphomas.

[18F]-Fluorodeoxyglucose positron emission tomography (PET-[18F]-FDG) is the gold standard for imaging systemic lymphomas, but its application in primary CNS lymphoma is compromised by the limited specificity of brain fixations and the high uptake of [18F]-FDG in healthy brain tissue.

[18F]-Fludarabine is a new radiopharmaceutical developed for PET imaging of lymphomas. Preclinical studies indicate a restricted binding specificity to lymphoid tissue compared to [18F]-FDG and an ability to detect residual lymphoma disease after treatment. A pilot study in humans shows good agreement of its binding with tumor sites in systemic lymphoma and superior tumor contrast to [18F]-FDG. Finally, a recent preclinical study shows a binding ratio in brain lymphoma 3 times higher than that of healthy brain tissue in mouse models of primary CNS lymphoma, whereas in mouse models of high-grade glial tumors, the binding level is very low, comparable to that of healthy tissue (background). Investigators hypothesize that [18F]-Fludarabine could be the radiopharmaceutical of choice for the diagnosis and monitoring of primary CNS lymphomas in PET.

The main objective of the study is to characterize the cerebral distribution and [18F]-Fludarabine uptake in newly-diagnosed primary CNS lymphomas before surgery, chemotherapy or radiotherapy, using PET-MR imaging.

Description:

Monocenter, open, uncontrolled and non-randomized pilot study designed to evaluate the uptake of [18F]-Fludarabine in 16 patients with newly diagnosed CNS lymphoma at initial diagnosis, before treatment using hybrid PET/MR system.

Main objective: to characterize the brain distribution and tumoral uptake in CNS lymphoma before treatment. The secondary objectives are to compare PET-[18F]-Fludarabine results with those of morphological MRI with and without gadolinium injection, diffusion and perfusion MRI, proton-spectroscopy, histological or cytological diagnosis, and brain [18F]-FDG PET imaging.

Patient screening includes a clinical and neurological examination, diagnostic MRI, biological examination, [18F]-FDG PET examination to exclude systemic lymphoma, histological/cytological diagnosis of brain lymphoma. Once informed consent is obtained, one brain PET with [18F]-Fludarabine (4 MBq/kg) combined with simultaneous multiparametric MR sequences is scheduled.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: June 15, 2025
• Est. primary completion date: May 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients aged = 18 years

• Diagnosis of newly diagnosed high-grade CNS lymphoma (with histological and/or cytological confirmation)

• Patient naive to chemotherapy, or radiotherapy treatment for CNS lymphoma

• Contrast-enhanced intracranial mass greater than or equal to 1 cm longest axis

• Karnofsky index = 40

• No systemic lymphoma on [18F]-FDG PET/CT

• Creatinine clearance = 30 mL/min

• Social security affiliation (excluding AME)

• Signature of the informed consent by the patient or by a legal representative or the close relative if the patient is not able to do so

Exclusion Criteria:

• Hypersensitivity to the active substance, to any of the excipients or to any of the components of [18F]-Fludarabine

• Previous treatment for primary central nervous system lymphoma

• Isolated primary vitro-retinal lymphoma

• Isolated CNS relapse of a systemic lymphoma

• Other active cancer except basal cell carcinoma of the skin and/or cervical cancer in situ

• Immunosuppression (organ transplant in particular)

• Positive HIV serology

• Presence of another progressive pathology that is life-threatening in the short term

• Treatment with dipyridamole

• History of allergy to gadolinium chelates (DOTAREM®)

• Absolute contraindication to MRI (pacemaker, cochlear implant ...), to the administration of gadolinium

• Patient of childbearing potential without effective contraception, breastfeeding or pregnant

• Severe cognitive impairment incompatible with good cooperation in the PET-MRI examination

• Patient with pain or restlessness unable to remain motionless in supine position for 60 minutes

• Weight > 100 Kg

• Patient deprived of liberty or under legal protection (guardianship or curatorship)

• Ongoing participation in another interventional research protocol. Participation in research of a non-interventional type is authorized.

Related Conditions & MeSH terms

• Lymphoma
• Primary Central Nervous System Lymphoma

Intervention

Drug:
• PET-MRI
[18F]-Fludarabine imaging in the diagnostic workup of primary central nervous system lymphomas: a PET-MRI pilot study

Locations

Country	Name	City	State
France	Hôpital Pitié Salpêtrière	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measurements of [18F]-Fludarabine uptake in tumoral lesions and normal tissue using SUV, tumor/normal tissues ratios	Standardized measurement of [18F]-Fludarabine uptake (SUV) in tumor will be done on PET imaging superimposed on post gadolinium MRI.	15 days
Secondary	Cerebral distribution of [18F]-Fludarabine in healthy and tumoral tissues	[18F]-Fludarabine time activity curves will be generated in normal and tumoral tissues with dynamic PET acquisition	15 days
Secondary	Temporal activity curves of [18F]-Fludarabine in healthy and tumoral tissues	[18F]-Fludarabine time activity curves will be generated in normal and tumoral tissues with dynamic PET acquisition	15 days
Secondary	Tumor SUVmax, tumor/healthy tissue ratio in PET- [18F]-FDG	Tumoral uptake in [18F]-FDG brain PET and brain [18F]-Fludarabine will be compared as well as contrast to normal uptake	15 days
Secondary	Volumes of contrast enhancement in post-gadolinium T1-weighted MR sequence	Tumor uptake delimitation will be compared to contrast enhancement limits	15 days
Secondary	Hypersignal in diffusion-weighted sequence and apparent diffusion coefficient (ADC)	Tumor volume on brain PET will be compared to hypersignal volume on T2-weighted FLAIR sequence	15 days
Secondary	Tumor perfusion, capillary permeability in perfusion weighted MRI	[18F]-Fludarabine uptake in tumor will be analyzed in light of tumor perfusion on PET superimposed on perfusion sequence	15 days
Secondary	Metabolite ratios in spectroscopy	[18F]-Fludarabine uptake in tumor will be analyzed in light of metabolites profile in proton-spectroscopy	15 days