Using a new PET imaging agent for staging marginal zone lymphoma

A Pivotal Phase 3 Clinical Trial to Assess the Diagnostic Performance and Safety of [68Ga]Ga-PentixaFor ([68Ga]Ga-PTF), a Positron Emission Tomography (PET) Imaging Agent, Versus [18F]FDG PET/CT Imaging, for Staging of Patients with Confirmed Marginal Zone Lymphoma Exemplary for CXCR4-positive Malignant Lymphomas: a Prospective, International, Multi-center, Comparative, Randomized, Cross-over, Open-label Lymphoma Diagnostic Trial

This study is testing a new PET imaging agent to see if it can better stage marginal zone lymphoma compared to the standard imaging method.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 148 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: Pentixapharm AG (Industry-sponsored)
• Locations: 12 sites (Innsbruck and 11 other locations)
• Trial ID: NCT06125028 on ClinicalTrials.gov

What this trial studies

This pivotal international trial aims to compare the diagnostic performance and safety of the PET imaging agent [68Ga]Ga-PentixaFor against the standard [18F]FDG PET/CT imaging in patients with confirmed marginal zone lymphoma. The study will be conducted in multiple centers and will involve a randomized, cross-over design to ensure robust data collection. Patients will be assessed for their staging of lymphoma, focusing on those with CXCR4-positive malignancies. The trial will also evaluate the safety profile of the new imaging agent.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a histologically confirmed diagnosis of treatment-naïve marginal zone lymphoma.

Not a fit: Patients with prior treatment for marginal zone lymphoma or those with other types of lymphoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more accurate and safer imaging option for staging marginal zone lymphoma, potentially leading to better treatment outcomes.

How similar studies have performed: Other studies have shown promising results with novel PET imaging agents, suggesting potential for success in this approach.

Eligibility criteria

Inclusion criteria:

All patients must meet all of the following criteria:

1. Signed informed consent from the patient.
2. Patients of either gender, aged ≥ 18 years.
3. Patients with a histologically proven diagnosis of marginal zone lymphoma (MZL) according to the World Health Organization (WHO) classification of lymphoid neoplasms. Patients must have a biopsy-proven nodal, extranodal, or splenic MZL (at the time of enrolment, the CXCR4 expression status will be unknown).
4. Treatment-naïve.
5. Negative pregnancy test in women capable of child-bearing and their agreement to use highly effective contraception for 1 month after the last dose of \[68Ga\]Ga-PTF and \[18F\]FDG.
6. For male patients whose partner is of child-bearing potential: The patient is willing to ensure that he and his partner use effective contraception for 1 month after the last dose of \[68Ga\]Ga-PTF and \[18F\]FDG.
7. Acceptable organ function, as evidenced by the following laboratory data:

   1. No renal impairment: Estimated glomerular filtration rate (eGFR) \> 30 mL/min/1.73 m2or creatinine clearance \> 60 mL/min by the Cockcroft-Gault equation or equivalent
   2. Total bilirubin ≤ 1.5 × ULN (upper limit of normal)
   3. Serum albumin ≥ 2.5 g/dL.
   4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN or ≤ 5 × ULN in the presence of liver metastases
   5. International normalized ratio (INR) \< 1.3 or ≤ institutional ULN.
8. Life expectancy ≥ 12 weeks as estimated by the Investigator.
9. The patient must not have undergone any physical or pharmacological intervention with curative or palliative intent between the time of any of the diagnostic measures and the \[68Ga\]Ga-PTF PET/CT and \[18F\]FDG PET/CT scan.

Exclusion criteria:

Patients will be excluded if one or more of the following criteria are met:

1. Known hypersensitivity to any active pharmaceutical agent or constituent of the \[68Ga\]Ga-PTF and/or \[18F\]FDG investigational products.
2. Inability to lie still for the entire imaging time.
3. Any severe acute or active chronic infection, as judged by the Investigator, at the time of screening or within two months prior to screening that may interfere with the diagnostic properties of \[68Ga\]Ga-PTF PET/CT and/or \[18F\]FDG PET/CT imaging.
4. Patients with plasma glucose levels higher than 11 mmol/L or 200 mg/dL prior to \[18F\]FDG administration.
5. Administration of any anti-cancer therapy within 1 month prior to study entry.
6. Patients with complete resection of all tumor lesion(s).
7. Administration of another investigational medicinal product within 30 days or within 5 terminal elimination half-lives of previous investigational medicinal product, whichever is longer, prior to study entry.
8. Current greater than grade 2 toxicity from any reason, per US-NCI "Common Terminology Criteria for Adverse Events v5.0" (NCI CTCAE 2017) except if tumor-related.
9. Pregnant or breast-feeding women.
10. Concomitant prohibited treatment which may interfere with \[68Ga\]Ga-PTF PET/CT imaging (systemic corticosteroids) administered within the last 1 month prior to study start.
11. Colony-stimulating factor (CSF) therapy within 5 days prior to \[18F\]FDG PET/CT examination.
12. Any recent myocardial infarction, stroke, or osteomyelitis within two months prior screening.
13. \[18F\]FDG PET/CT imaging or \[68Ga\]Ga-PTF PET imaging performed prior to study entry.
14. Judged by the referring physician as not mentally or as not physically fit to understand and comply with protocol-related interventions and procedures (e.g., medically retarded, body weight \> 180 kg for PET scanner).
15. Body weight of less than 48 kg.
16. Any other concurrently active neoplasia, or other disease who could jeopardize study safety or data.

Where this trial is running

Innsbruck and 11 other locations

• Medizinische Universität Innsbruck — Innsbruck, Austria (Recruiting)
• CHU de Bordeaux — Bordeaux, France (Recruiting)
• CHU La Timone — Marseille, France (Recruiting)
• CHU de Nantes — Nantes, France (Recruiting)
• Hôpital Cochin — Paris, France (Recruiting)
• Universitätsklinikum Essen — Essen, Germany (Recruiting)
• Universitätsklinikum Würzburg — Würzburg, Germany (Recruiting)
• IRCCS Azienda Ospedaliero-Universitaria di Bologna — Bologna, Italy (Recruiting)
• L'IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l — Meldola, Italy (Recruiting)
• Ospedale San Raffaele S.r.l. — Milano, Italy (Recruiting)
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Rome, Italy (Recruiting)
• Clinica Universidad de Navarra — Pamplona, Navarra, Spain (Recruiting)

Study contacts

• Principal investigator: Andreas Buck, Prof. Dr. — University Hospital Würzburg, Department of Nuclear Medicine
• Study coordinator: Egenberger Brigitte

Conditions Marginal Zone Lymphoma