[68Ga]Ga-PentixaFor positron emission tomography for improved risk and disease assessment in myeloma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Of Antwerp

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], Diseases [C] - Neoplasms [C04]

Trial duration

20 Sep 2024 → ongoing

Decision date (initial)

2023-07-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

FWO-TBM

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Diagnosis

To evaluate the proportion of false negative (FN) PET results for [68Ga]Ga-PentixaFor PET/AC-CT at baseline.

Conditions and MedDRA coding

Multiple Myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. All patients who are eligible to start the IMMPROVED study (and signed for participation) can be included in this exploratory study.
2. Transplant-eligible newly diagnosed multiple myeloma based on current IMWG criteria and scheduled for induction chemotherapy followed by ASCT (Inclusion criteria of the IMMPROVED study). patients can therefore also be included after ASCT, prior to lenalidomide maintenance.
3. Baseline 18F-FDG PET/CT scan (Inclusion criteria of the IMMPROVED study)
4. WHO performance status 0-2 (WHO > 2 can be allowed if the patient is fit for intensive chemotherapy based on the opinion of the physician). (Inclusion criteria of the IMMPROVED study)
5. 18 years of older (Inclusion criteria of the IMMPROVED study)
6. Signed informed consent.
7. Life expectancy > 12 months, based on clinical judgement (Inclusion criteria of the IMMPROVED study)
8. Baseline [68Ga]Ga-PentixaFor PET/CT should be scheduled before starting induction chemotherapy. Exception for patients who will be included after ASCT, but prior to lenalidomide maintenance therapy. (Specific for this study).
9. An interval of maximum 14 days is allowed between the 18F-FDG and [68Ga]Ga-PentixaFor PET/CT scans (Specific for this study).

Exclusion criteria 4

1. Any physical or physiological condition that may affect adherence to the study protocol, e.g severe claustrophobia or the inability to lie still for 30 minutes.
2. History of concomitant presence of any other malignancy, except for: non-melanoma skin cancer, carcinoma in situ of the cervix, or any other effectively treated malignancy that has been in remission for >5 years or that is highly likely to be cured at the time of enrollment.
3. Pregnant or breastfeeding
4. Refusal or inability to provide written informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. to make an evaluation of the proportion of false negative (FN) PET results for[68Ga]Ga-PentixaFor PET/AC-CT at baseline. Whereas a FN scan is defined as the absence of a focal lesion suspected for myeloma (higher than local background for [68Ga]Ga-PentixaFor) and/or the absence of diffuse bone marrow uptake in a patient with proven multiple myeloma according to the IMWG criteria

Secondary endpoints 8

1. Comparison of the proportion of false negative (FN) PET results between 18F-FDG/LDCT and [68Ga]Ga-PentixaFor PET/AC-CT at baseline. Whereas a FN scan for both tracers is defined as the absence of a focal lesion suspected for myeloma (higher than local background for [68Ga]Ga-PentixaFor, and DS4 for 18F-FDG) and/or the absence of diffuse bone marrow uptake in a patient with proven multiple myeloma according to the IMWG criteria.
2. Comparison of the (number of) lesions for both tracers: (1) Perform an inter-observer agreement analysis for image quality and lesions conspicuity and evaluate the applicability of Deauville score (DS) in [68Ga]Ga-PentixaFor PET scans. The readers will score global image quality, lesion conspicuity and diagnostic confidence.
3. Comparison of the (number of) lesions for both tracers: (2) Lesion detection rate analysis on patient level and on organ level (lymph nodes, bone marrow and other extra-medullar disease) by calculating the difference in detection ratio of 18F-FDG PET/LDCT and [68Ga]Ga-PentixaFor PET/AC-CT, i.e. the differential detection ratio (DDR). This will be done based on a lesion detection rate analysis. The fraction of the lesions detected by one tracer is the detection Ratio (DR).
4. Comparison of the (number of) lesions for both tracers: (3) Semi-quantitative analysis of radiotracer uptake in lesions to quantify lesion intensity (maximum tracer uptake) and contrast (tumor to local background) for both tracers. Standardized uptake value (SUV) measurements will be performed: SUVmax for lesions and SUVmean for local background areas will be determined. Lesion uptake, in terms of SUVmax and tumor-to-background ratio (TBR), will be compared for both tracers.
5. To quantify [68Ga]Ga-PentixaFor uptake based on dynamic PET studies and full kinetic modelling. To evaluate if simplified measures like SUV are a valid alternative for clinical practice or more complicated methods are required.
6. Evaluation of the prognostic value of [68Ga]Ga-PentixaFor PET tracer in multiple myeloma patients. Is there a difference in clinical outcome based on PET positivity for [68Ga]Ga-PentixaFor tracer, PET positivity for 18F-FDG tracer or PET positivity for both tracers (PET positivity at baseline)?
7. Evaluation of different PET features (application of IMPeTUs, SUVmax, TBR, LDR, Radiomics) to be used for prognosis. Can these features be linked to a higher risk group (based on R-ISS and ISS risk classification). Will the use of a different PET tracer, [68Ga]Ga-PentixaFor vs 18F-FDG, have an impact on the patient’s classification in a risk group?
8. Sub-analysis pre and post therapy We will evaluate whether differences are visible pre and post therapy for the radiotracers. A comparison of the baseline PET scan with PET scans after therapy will be made. This will be done for both tracers. An evaluation of the applicability of the tracers for a post therapy scan will be made.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Of Antwerp

Sponsor organisation

University Of Antwerp

Address

Universiteitsplein 1

City

Antwerp

Postcode

2610

Country

Belgium

Scientific contact point

Organisation

University Of Antwerp

Contact name

Sigrid Stroobants

Public contact point

Organisation

University Of Antwerp

Contact name

Sigrid Stroobants

Locations

2 EU/EEA countries · 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 2 files

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

Application history

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