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Evaluation of PET 18F-Fludarabine for the Initial Assessment and End-treatment of Symptomatic Multiple Myeloma Patients (Myelofludate)

Primary Purpose

Myeloma

Status
Not yet recruiting
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
18F-Fludarabine
Sponsored by
Nantes University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Myeloma

Eligibility Criteria

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

Inclusion Criteria:

  • Symptomatic MM in the first line in patients who are not candidates for autologous bone marrow transplantation.
  • Patients eligible for one of the treatments considered as standard in a patient who is not eligible for autograft, according to ESMO's European recommendations
  • MM with measurable disease either by the serum evaluation of the monoclonal component or by the determination of free light chains (serum or urinary).
  • Patient affiliated with a social insurance scheme
  • The patient must understand and voluntarily sign the informed consent form
  • Women of childbearing potential must have a serum pregnancy test (performed within 2 days before each PET scan.)
  • Women of childbearing potential must use an effective contraceptive method throughout the course of the study and for 30 days after the last PET.
  • Male patients (vasectomised or not) with a pregnant partner or a partner of childbearing potential must use a condom and a spermicide until 90 days after the last PET.
  • HIV serology known to be negative
  • Karnofsky ≥ 70 or ECOG 0-1

Exclusion Criteria:

  • Age under 18 years
  • Pregnancy or breastfeeding
  • Male or female refusing birth control conditions
  • Primary AL amyloidosis and myeloma complicated by amyloidosis
  • Neutropenia <1000 PN / mm3
  • Thrombocytopenia <70,000 / mm3
  • Hepatic impairment: bilirubin> 35μmol / L and SGOT, SGPT, alkaline phosphatase greater than 3 N
  • Renal impairment defined by creatinine clearance <50 ml / min
  • History of other malignancies with the exception of basal cell carcinoma and stage I cervical cancer
  • Severe active infection
  • Active infection with known hepatitis B or C virus.
  • Patient with insulin-dependent or non-insulin-dependent diabetes mellitus.
  • Intolerance or known allergy to any of the study drugs or any of its analogues
  • Psychiatric illness that may interfere with participation in the study
  • Patient under safeguard of justice
  • Intellectual inability to sign informed consent
  • Persons protected by law

Sites / Locations

  • CHU d'Angers
  • CHU de Brest
  • CHU de Caen
  • CHU de Nantes
  • Centre Eugène Marquis
  • CHU de Rennes
  • CHU de Tours

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fludatep

Arm Description

PET with 18F-Fludarabine

Outcomes

Primary Outcome Measures

Detection of sensitivity of the lesions (osseous and extra-osseous) of 18Fludarabine PET (FludaTEP)
The sensitivity of the initial FludaTEP will be evaluated using an optimal reading mode lesion analysis (ie by consensus of experts) by defining : True positive: positive lesion with 18F-Fludarabine and positive with PET-FDG or MRI or positive lesion with 18-F-Fludarabine, negative with PET-FDG and MRI, but confirmed by further complementary imaging (CT) or histological examination, or confirmed at follow-up False negative: -negative lesion with 18F-Fludarabine and positive FDG-PET and / or MR Lesions positivity in PET-FDG and MRI will be assessed by central reading done by consensus of experts. Lesions positivity with 18F-Fludarabine will be defined by central reading assessed by 2 nuclear physicians experts in hematology with no access to the other exams' results.

Secondary Outcome Measures

To evaluate the specificity and the positive and negative predictive values of the FludaTEP for the initial assessment through an optimal reading mode.
The specificity, positive predictive value (PPV) and negative predictive value (NPV) of the FludaTEP for the initial assessment will be assessed through an optimal reading mode lesion analysis (ie by consensus of experts) using same true positive and false positive définitions as for the main endpoint and defining: -positive lesion with 18F-Fludarabine but not found or confirmed on an histological examination, or other imaging technique (PET-FDG, MRI +/- Scan) or at follow-up True negative: -negative lesion with 18F-Fludarabine and negative with FDG-PET and MRI
To evaluate the sensitivity, specificity, and positive and negative predictive values of the FludaTEP for the initial balance according to the local reading
The specificity, positive predictive value (PPV) and negative predictive value (NPV) of the FludaTEP for the initial balance will be evaluated through lesion analysis based on the local reading investigator center reading using definitions of VP, VN, FP, and FN described above.
To evaluate the prognostic impact of FDG-PET and FludaTEP on the number of lesions detected by each imaging technique in a population of MM patients in the 1st line therapeutic but not candidates for marrow autograft.
The prognostic impact of FDG-PET and FludaTEP as a function of the number of lesions detected by each imaging technique will be evaluated by evaluating the impact of these data on progression-free survival and overall survival. Progression-free survival is defined as the time between the beginning of treatment of the disease and relapse or progression. Overall survival is defined as the time between the start of treatment and death.
To evaluate the prognostic impact of FludaTEP on the initial assessment and for the end-of-treatment therapeutic evaluation
The prognostic impact of FludaTEP on the initial assessment and for the end-of-treatment therapeutic evaluation will be determined by evaluating the impact of a decrease and a negation of the signal in imaging on an increase in progression-free survival and overall survival.
Evaluate in a population of MM patients the existence of a correlation between the 18Fludarabine and FDG uptake intensities
Correlations between the 18Fludarabine and FDG uptake intensities assessed by SUVs and the quantitative expression of markers measured in flow cytometry and cytogenetic data (in particular the expression of the coding gene for hexokinases) will be measured using Spearman's correlation coefficient.
Evaluate in a population of MM patients the existence of a correlation between the 18Fludarabine and FDG uptake intensities and the cytogenetic data Tolerance to 18F-Fludarabine
Tolerance to 18F-Fludarabine will be evaluated by clinical monitoring during 2 hours following the 18F-Fludarabine injection. Clinical data will be taken prior to the 18F-Fludarabine injection, prior to the data capture at 60min and after the last data capture.

Full Information

First Posted
July 20, 2018
Last Updated
December 24, 2021
Sponsor
Nantes University Hospital
Collaborators
Cyceron
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1. Study Identification

Unique Protocol Identification Number
NCT03832127
Brief Title
Evaluation of PET 18F-Fludarabine for the Initial Assessment and End-treatment of Symptomatic Multiple Myeloma Patients
Acronym
Myelofludate
Official Title
Exploratory Study Evaluating the Interest of PET to 18F-Fludarabine for the Initial Assessment and End-treatment Evaluation of Patients With Symptomatic Multiple Myeloma in the First Line of Treatment, Not Candidates for Marrow Autograft
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 1, 2022 (Anticipated)
Primary Completion Date
April 1, 2024 (Anticipated)
Study Completion Date
April 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nantes University Hospital
Collaborators
Cyceron

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The objective of this exploratory study is to evaluate, for the first time, the sensitivity of 18F-Fludarabine to the initial diagnosis of MM compared to FDG-PET and MRI. The interest of this molecule will also be investigated as part of the end-of-treatment therapeutic evaluation.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Fludatep
Arm Type
Experimental
Arm Description
PET with 18F-Fludarabine
Intervention Type
Drug
Intervention Name(s)
18F-Fludarabine
Intervention Description
Two PET with 18F-Fludarabine : one at Baseline, the second one at the end of treatment of myeloma
Primary Outcome Measure Information:
Title
Detection of sensitivity of the lesions (osseous and extra-osseous) of 18Fludarabine PET (FludaTEP)
Description
The sensitivity of the initial FludaTEP will be evaluated using an optimal reading mode lesion analysis (ie by consensus of experts) by defining : True positive: positive lesion with 18F-Fludarabine and positive with PET-FDG or MRI or positive lesion with 18-F-Fludarabine, negative with PET-FDG and MRI, but confirmed by further complementary imaging (CT) or histological examination, or confirmed at follow-up False negative: -negative lesion with 18F-Fludarabine and positive FDG-PET and / or MR Lesions positivity in PET-FDG and MRI will be assessed by central reading done by consensus of experts. Lesions positivity with 18F-Fludarabine will be defined by central reading assessed by 2 nuclear physicians experts in hematology with no access to the other exams' results.
Time Frame
Before treatment
Secondary Outcome Measure Information:
Title
To evaluate the specificity and the positive and negative predictive values of the FludaTEP for the initial assessment through an optimal reading mode.
Description
The specificity, positive predictive value (PPV) and negative predictive value (NPV) of the FludaTEP for the initial assessment will be assessed through an optimal reading mode lesion analysis (ie by consensus of experts) using same true positive and false positive définitions as for the main endpoint and defining: -positive lesion with 18F-Fludarabine but not found or confirmed on an histological examination, or other imaging technique (PET-FDG, MRI +/- Scan) or at follow-up True negative: -negative lesion with 18F-Fludarabine and negative with FDG-PET and MRI
Time Frame
Before treatment
Title
To evaluate the sensitivity, specificity, and positive and negative predictive values of the FludaTEP for the initial balance according to the local reading
Description
The specificity, positive predictive value (PPV) and negative predictive value (NPV) of the FludaTEP for the initial balance will be evaluated through lesion analysis based on the local reading investigator center reading using definitions of VP, VN, FP, and FN described above.
Time Frame
Before treatment
Title
To evaluate the prognostic impact of FDG-PET and FludaTEP on the number of lesions detected by each imaging technique in a population of MM patients in the 1st line therapeutic but not candidates for marrow autograft.
Description
The prognostic impact of FDG-PET and FludaTEP as a function of the number of lesions detected by each imaging technique will be evaluated by evaluating the impact of these data on progression-free survival and overall survival. Progression-free survival is defined as the time between the beginning of treatment of the disease and relapse or progression. Overall survival is defined as the time between the start of treatment and death.
Time Frame
After treatment
Title
To evaluate the prognostic impact of FludaTEP on the initial assessment and for the end-of-treatment therapeutic evaluation
Description
The prognostic impact of FludaTEP on the initial assessment and for the end-of-treatment therapeutic evaluation will be determined by evaluating the impact of a decrease and a negation of the signal in imaging on an increase in progression-free survival and overall survival.
Time Frame
Before and After treatment
Title
Evaluate in a population of MM patients the existence of a correlation between the 18Fludarabine and FDG uptake intensities
Description
Correlations between the 18Fludarabine and FDG uptake intensities assessed by SUVs and the quantitative expression of markers measured in flow cytometry and cytogenetic data (in particular the expression of the coding gene for hexokinases) will be measured using Spearman's correlation coefficient.
Time Frame
Before and After treatment
Title
Evaluate in a population of MM patients the existence of a correlation between the 18Fludarabine and FDG uptake intensities and the cytogenetic data Tolerance to 18F-Fludarabine
Description
Tolerance to 18F-Fludarabine will be evaluated by clinical monitoring during 2 hours following the 18F-Fludarabine injection. Clinical data will be taken prior to the 18F-Fludarabine injection, prior to the data capture at 60min and after the last data capture.
Time Frame
Before and After treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Symptomatic MM in the first line in patients who are not candidates for autologous bone marrow transplantation. Patients eligible for one of the treatments considered as standard in a patient who is not eligible for autograft, according to ESMO's European recommendations MM with measurable disease either by the serum evaluation of the monoclonal component or by the determination of free light chains (serum or urinary). Patient affiliated with a social insurance scheme The patient must understand and voluntarily sign the informed consent form Women of childbearing potential must have a serum pregnancy test (performed within 2 days before each PET scan.) Women of childbearing potential must use an effective contraceptive method throughout the course of the study and for 30 days after the last PET. Male patients (vasectomised or not) with a pregnant partner or a partner of childbearing potential must use a condom and a spermicide until 90 days after the last PET. HIV serology known to be negative Karnofsky ≥ 70 or ECOG 0-1 Exclusion Criteria: Age under 18 years Pregnancy or breastfeeding Male or female refusing birth control conditions Primary AL amyloidosis and myeloma complicated by amyloidosis Neutropenia <1000 PN / mm3 Thrombocytopenia <70,000 / mm3 Hepatic impairment: bilirubin> 35μmol / L and SGOT, SGPT, alkaline phosphatase greater than 3 N Renal impairment defined by creatinine clearance <50 ml / min History of other malignancies with the exception of basal cell carcinoma and stage I cervical cancer Severe active infection Active infection with known hepatitis B or C virus. Patient with insulin-dependent or non-insulin-dependent diabetes mellitus. Intolerance or known allergy to any of the study drugs or any of its analogues Psychiatric illness that may interfere with participation in the study Patient under safeguard of justice Intellectual inability to sign informed consent Persons protected by law
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Caroline Bodet-Milin, MD
Phone
33240084136
Email
caroline.milin@chu-nantes.fr
Facility Information:
Facility Name
CHU d'Angers
City
Angers
ZIP/Postal Code
49100
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pacôme Fosse, MD
First Name & Middle Initial & Last Name & Degree
Pacôme Fosse, MD
Facility Name
CHU de Brest
City
Brest
ZIP/Postal Code
29000
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierre Yves Salaün, MD
First Name & Middle Initial & Last Name & Degree
Pierre Yvese Salaün, MD
Facility Name
CHU de Caen
City
Caen
ZIP/Postal Code
14000
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicolas Aide, MD
First Name & Middle Initial & Last Name & Degree
Nicolas Aide, MD
Facility Name
CHU de Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caroline Bodet-Milin, MD
First Name & Middle Initial & Last Name & Degree
Caroline bodet Mion, MD
Facility Name
Centre Eugène Marquis
City
Rennes
ZIP/Postal Code
35000
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne Devillers, MD
First Name & Middle Initial & Last Name & Degree
Anne Devillers, MD
Facility Name
CHU de Rennes
City
Rennes
ZIP/Postal Code
35000
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thierry Lamy, MD
First Name & Middle Initial & Last Name & Degree
Thierry Lamy, MD
Facility Name
CHU de Tours
City
Tours
ZIP/Postal Code
37000
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Joao Santiago-Ribeiro, MD
First Name & Middle Initial & Last Name & Degree
Maria Joao Santiago-Ribeiro, MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Evaluation of PET 18F-Fludarabine for the Initial Assessment and End-treatment of Symptomatic Multiple Myeloma Patients

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