[68Ga]Ga-PentixaFor-PET Imaging for Staging of 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 will be a pivotal prospective prospective, international, multi-center, comparative, randomized, cross-over, open-label lymphoma diagnostic trial to assess the diagnostic performance and safety of the positron emission tomography (PET) imaging agent [68Ga]Ga-PTF) , versus [18F]FDG PET/CT imaging, for staging of patients with confirmed marginal zone lymphoma exemplary for CXCR4-positive malignant lymphomas.

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.