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

Primary Purpose

Primary Central Nervous System Lymphoma

Status

Not yet recruiting

Phase

Phase 1

Locations

France

Study Type

Interventional

Intervention

PET-MRI

About this trial

This is an interventional diagnostic trial for Primary Central Nervous System Lymphoma focused on measuring [18F]-Fludarabine, PET-MRI, Primary Central Nervous System Lymphomas

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Hôpital Pitié Salpêtrière

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PET-RMI

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

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

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

Volumes of contrast enhancement in post-gadolinium T1-weighted MR sequence

Tumor uptake delimitation will be compared to contrast enhancement limits

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

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

Metabolite ratios in spectroscopy

[18F]-Fludarabine uptake in tumor will be analyzed in light of metabolites profile in proton-spectroscopy

Full Information

NCT ID

NCT05390814

First Posted

May 20, 2022

Last Updated

May 20, 2022

Sponsor

Assistance Publique - Hôpitaux de Paris

1. Study Identification

Unique Protocol Identification Number

NCT05390814

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

June 15, 2022 (Anticipated)

Primary Completion Date

May 30, 2023 (Anticipated)

Study Completion Date

June 15, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed Description

Monocenter, open, uncontrolled and non-randomized pilot study designed to evaluate the uptake of [18F]-Fludarabine in 8 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Primary Central Nervous System Lymphoma

Keywords

[18F]-Fludarabine, PET-MRI, Primary Central Nervous System Lymphomas

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

8 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

PET-RMI

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

PET-MRI

Intervention Description

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

Primary Outcome Measure Information:

Title

Measurements of [18F]-Fludarabine uptake in tumoral lesions and normal tissue using SUV, tumor/normal tissues ratios

Description

Standardized measurement of [18F]-Fludarabine uptake (SUV) in tumor will be done on PET imaging superimposed on post gadolinium MRI.

Time Frame

15 days

Secondary Outcome Measure Information:

Title

Cerebral distribution of [18F]-Fludarabine in healthy and tumoral tissues

Description

[18F]-Fludarabine time activity curves will be generated in normal and tumoral tissues with dynamic PET acquisition

Time Frame

15 days

Title

Temporal activity curves of [18F]-Fludarabine in healthy and tumoral tissues

Description

[18F]-Fludarabine time activity curves will be generated in normal and tumoral tissues with dynamic PET acquisition

Time Frame

15 days

Title

Tumor SUVmax, tumor/healthy tissue ratio in PET- [18F]-FDG

Description

Tumoral uptake in [18F]-FDG brain PET and brain [18F]-Fludarabine will be compared as well as contrast to normal uptake

Time Frame

15 days

Title

Volumes of contrast enhancement in post-gadolinium T1-weighted MR sequence

Description

Tumor uptake delimitation will be compared to contrast enhancement limits

Time Frame

15 days

Title

Hypersignal in diffusion-weighted sequence and apparent diffusion coefficient (ADC)

Description

Tumor volume on brain PET will be compared to hypersignal volume on T2-weighted FLAIR sequence

Time Frame

15 days

Title

Tumor perfusion, capillary permeability in perfusion weighted MRI

Description

[18F]-Fludarabine uptake in tumor will be analyzed in light of tumor perfusion on PET superimposed on perfusion sequence

Time Frame

15 days

Title

Metabolite ratios in spectroscopy

Description

[18F]-Fludarabine uptake in tumor will be analyzed in light of metabolites profile in proton-spectroscopy

Time Frame

15 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Aurélie KAS, Pr

Phone

01 42 17 62 81

aurelie.kas@aphp.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Aurélie KAS, Pr

Organizational Affiliation

Assistance Publique - Hôpitaux de Paris

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hôpital Pitié Salpêtrière

City

Paris

ZIP/Postal Code

75013

Country

France

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Aurélie KAS, Pr

Phone

01 42 17 62 81

aurelie.kas@aphp.fr

12. IPD Sharing Statement

Learn more about this trial

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

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