Relevance Evaluation of [68Ga]Ga-PentixaFor for Initial Staging and Detection of Minimal Residual Disease in Multiple Myeloma Patients.

Study Overview
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Brief Summary
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The aim of our study is to confirm the relevance of PET using [68Ga]Ga-PentixaFor ligand, in comparison with FDG, for initial staging and detection of minimal residual disease in multiple myeloma patients eligible for autologous stem cell transplantation less than 66 years. The prognostic value of positive CXCR4 expression will also be assessed and [68Ga]Ga-PentixaFor/FDG discordances explored.

Official Title
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Exploratory Study Evaluating the Relevance of [68Ga]Ga-PentixaFor for Initial Staging and Detection of Minimal Residual Disease in Multiple Myeloma Patients Eligible for Autologous Stem Cell Transplantation Less Than 66 Years Included in the Prospective IFM 2020-02.

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: [68Ga]Ga-PentixaFor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria are identical to inclusion criteria in MIDAS study (EudraCT Number: 2020-005216-21, ClinicalTrials.gov Identifier: NCT04934475) . Exclusion Criteria: Non inclusion criteria are identical to non inclusion criteria in MIDAS study (EudraCT Number: 2020-005216-21, ClinicalTrials.gov Identifier: NCT04934475) added with: eGFR < 50 ml/min by MDRD or CKDEPI. Previous or concurrent second malignancy except for adequately treated basal cell carcinoma of the skin, curatively treated in situ carcinoma of the cervix, curatively treated solid cancer, with no evidence of disease for at least 2 years. Patient with uncontrolled insulin-dependent or non-insulin-dependent diabetes mellitus.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [68Ga]Ga-PentixaFor<br> | Drug: [68Ga]Ga-PentixaFor<br>* Tomography by Emission of Positons (PET) with the radiopharmaceutic [68Ga]Ga-PentixaFor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity | To determine the sensitivity of [68Ga]Ga-PentixaFor-PET to detect Multiple Myeloma lesions [Bone marrow (BM) lesions and/or extra-medullary disease (EMD)] at the time of initial diagnosis in high risk MM patients included in the MIDAS study. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Specificity, positive predictive value (PPV) and negative predictive value (NPV) of [68Ga]Ga-PentixaFor-PET. | The specificity (PPV and NPV) of [68Ga]Ga-PentixaFor-PET at the time of initial diagnosis will be assessed by patient and lesion analysis using the same definitions of TP and FN as for the primary objective. | 1 month | 
| Prognostic impact of FDG-PET and of [68Ga]Ga-PentixaFor-PET depending on the uptake detected by each imaging technique. | The prognostic impact of FDG-PET and [68Ga]Ga-PentixaFor-PET based on the number of lesions detected of uptake by each imaging technique will be evaluated by assessing the impact of these data on the PFS and OS. PFS is defined as the time from the start of treatment to relapse or progression. OS is defined as the time from the start of first treatment to death. | 1 month | 
| Discrepancies rate between FDG-PET and [68Ga]Ga-PentixaFor-PET and factors associated with. | * We will consider as discordant a lesion positive by FDG-PET but negative by [68Ga]Ga-PentixaFor-PET and/or a lesion negative by FDG-PET but positive by [68Ga]Ga-PentixaFor-PET. | 1 month and 6 months | 
| Correlation between FDG-PET and [68Ga]Ga-PentixaFor-PET uptakes evaluated by SUV. | [68Ga]Ga-PentixaFor and FDG uptakes assessed by SUV. | 1 month | 
| Correlation between FDG-PET and [68Ga]Ga-PentixaFor-PET uptakes evaluated by the RNAseq data evaluated on the myelogram. | [68Ga]Ga-PentixaFor and FDG uptakes assessed by the quantitative expression of biological markers on myelogram (including expression of the gene coding for hexokinases). | 1 month | 
| Prognostic impact of FDG-PET and [68Ga]Ga-PentixaFor-PET depending on the positivity, number and intensity of uptake detected by each imaging technique. | The prognostic impact of [68Ga]Ga-PentixaFor-PET after therapy will be determined by evaluating the impact of a decrease uptake and/or a normalization of images on PFS and OS. | 6 months | 
| Link between FDG-PET, [68Ga]Ga-PentixaFor-PET results and minimal residual disease evaluated by NGS. | FDG-PET, [68Ga]Ga-PentixaFor-PET results (positive/negative) and minimal residual disease evaluated by NGS (positive/negative). | 6 months | 
| Tolerance of [68Ga]Ga-PentixaFor-PET. | Tolerance of [68Ga]Ga-PentixaFor will be assessed by clinical monitoring of the patient for 1 hour after [68Ga]Ga-PentixaFor injection. Clinical data will be collected prior and 5/10 min after [68Ga]Ga-PentixaFor injection before acquisition (at 60 min after the injection) and at the end of acquisition (at approximately 80 min after the injection). | 1 month and 6 months |