Exploratory study evaluating the relevance of [68Ga]Ga-PentixaFor for initial staging and therapeutic evaluation of symptomatic multiple myeloma patients in first line treatment or in relapse.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nantes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

Trial duration

21 Sep 2021 → ongoing

Decision date (initial)

2024-09-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-516752-18-00

EudraCT number

2020-004268-24

ClinicalTrials.gov

NCT04561492

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

To determine the sensitivity of [68Ga]Ga-PentixaFor-PET to detect Multiple Myeloma (MM) lesions [Bone marrow (BM) lesions and/or extra-medullary disease (EMD) ] at the time of initial diagnosis or at relapse.

Secondary objectives 10

1. To determine at the time of initial diagnosis or at relapse, the specificity, positive predictive value (PPV) and negative predictive value (NPV) of [68Ga]Ga-PentixaFor-PET
2. To determine at the time of initial diagnosis or at relapse, the discrepancies rate between FDG-PET and [68Ga]Ga-PentixaFor-PET
3. To determine at the time of initial diagnosis or at relapse, the prognostic impact of FDG-PET and of [68Ga]Ga-PentixaFor-PET depending on the positivity, number and intensity of uptake detected by each imaging technique
4. To determine at the time of initial diagnosis or at relapse, factors associated with discrepancies between FDG-PET and [68Ga]Ga-PentixaFor-PET
5. To determine at the time of initial diagnosis or at relapse, the correlation between FDG-PET and [68Ga]Ga-PentixaFor-PET uptakes evaluated by SUV and the cytogenetic data evaluated on the myelogram (particularly the measurement of the expression of the gene coding for hexokinases)
6. To determine at the time of initial diagnosis or at relapse, tolerance of [68Ga]Ga-PentixaFor-PET
7. To determine at the time of therapeutic evaluation, the discrepancies rate between FDG-PET and [68Ga]Ga-PentixaFor-PET and if available their link with histology
8. To determine at the time of therapeutic evaluation, the prognostic impact of FDG-PET and [68Ga]Ga-PentixaFor-PET depending on the positivity, number and intensity of uptake detected by each imaging technique
9. To determine at the time of therapeutic evaluation, the link between FDG-PET, [68Ga]Ga-PentixaFor-PET results and minimal residual disease evaluated by flow cytometry
10. To determine at the time of therapeutic evaluation, tolerance of [68Ga]Ga-PentixaFor-PET

Conditions and MedDRA coding

Multiple myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age ≥ 18 years
2. Symptomatic MM patient according to IMWG criteria requiring first-line treatment or in relapse
3. Written and signed informed consent (obtained on the screening day at the latest and before any investigation)
4. ECOG (Eastern Cooperative Oncology Group) < 2
5. Patient affiliated to or beneficiary of the National Health Service

Exclusion criteria 10

1. HIV positive, active Hepatitis B or C
2. Childbearing or child breast feeding woman
3. Woman or man without effective contraceptive barrier if needed
4. eGFR < 50 ml/min by MDRD or CKDEPI
5. 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
6. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
7. Known active infection
8. Patient with uncontrolled insulin-dependent or non-insulin-dependent diabetes mellitus
9. Patient under guardianship or trusteeship
10. Patient under judicial protection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Sensitivity will be assessed by patient and lesion analysis by defining: o True positive (TP): - lesion positive with [68Ga]Ga-PentixaFor-PET and confirmed by another imaging method (FDG-PET/CT, CT scan or MRI) and follow-up or confirmed by histology. o False negative (FN): - lesion negative with [68Ga]Ga-PentixaFor-PET and positive by FDG-PET and confirmed by CT or MRI or histology, or confirmed by follow-up.

Secondary endpoints 9

1. At the time of initial diagnosis or at relapse, 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.
2. At the time of initial diagnosis or at relapse, the prognostic impact of FDG-PET and [68Ga]Ga-PentixaFor-PET based on the number of lesions detected and their intensity 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 treatment to death.
3. At the time of initial diagnosis or at relapse, 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
4. At the time of initial diagnosis or at relapse, [68Ga]Ga-PentixaFor and FDG uptakes assessed by SUV and the quantitative expression of biological markers on myelogram (including expression of the gene coding for hexokinases).
5. At the time of initial diagnosis or at relapse, tolerance of [68Ga]Ga-PentixaFor will be assessed by clinical monitoring of the patient for 1 hour after [68Ga]Ga-PentixaFor injection. Clinical data (heart rate, oxygen saturation and blood pressure) will be collected prior [68Ga]Ga-PentixaFor injection before acquisition (at 60 min) and at the end of acquisition (at approximately 80 min).
6. At the time of therapeutic evaluation, 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.
7. At the time of therapeutic evaluation, the prognostic impact of [68Ga]Ga-PentixaFor-PET after therapy will be determined by evaluating the impact of a decrease uptake and/or a normalisation of images on PFS and OS.
8. At the time of therapeutic evaluation, PET-FDG, [68Ga]Ga-PentixaFor-PET results (positive/negative) and minimal residual disease evaluated by flow cytometry (positive/negative).
9. At the time of therapeutic evaluation, tolerance of [68Ga]Ga-PentixaFor will be assessed by clinical monitoring of the patient for 1 hour after [68Ga]Ga-PentixaFor injection. Clinical data (heart rate, oxygen saturation and blood pressure) will be collected prior and 5/10 min after [68Ga]Ga-PentixaFor injection before acquisition (at 60 min) and at the end of acquisition (at approximately 80 min).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nantes

Sponsor organisation

Centre Hospitalier Universitaire De Nantes

Address

5 Allee De L Ile Gloriette, Cs 69301 Cs 69301

City

Nantes Cedex 1

Postcode

44093

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Pr Caroline BODET-MILN

Public contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Pr Caroline BODET-MILN

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications