[68Ga]Ga-PentixaFor-PET Imaging for Staging of Marginal Zone Lymphoma

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Marginal Zone Lymphoma

Intervention / Treatment
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* Drug: [68Ga]Ga-PentixaFor
* Drug: [18F]Fluorodeoxyglucose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form (ICF) from the patient. Patients of either gender, aged ≥ 18 years. Patients with a histologically proven diagnosis of MZL according to the World Health Organization 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). Treatment-naïve. 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. 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. Acceptable organ function, as evidenced by the following laboratory data: No renal impairment: Estimated glomerular filtration rate (eGFR) or creatinine clearance by the Cockcroft-Gault equation (or equivalent) should be > 30 mL/min/1.73 m2 or > 60 mL/min, respectively. Total bilirubin ≤ 1.5 × ULN (upper limit of normal) Serum albumin ≥ 2.5 g/dL Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN or ≤ 5 × ULN in the presence of liver metastases International normal ratio (INR) < 1.3 or ≤ institutional ULN. Life expectancy ≥ 12 weeks as estimated by the Investigator. 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: Known hypersensitivity to any active pharmaceutical agent or constituent of the [68Ga]Ga-PTF and/or [18F]FDG product. Inability to lie still for the entire imaging time. 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 or [18F]FDG PET/CT imaging. Patients presenting uncontrolled diabetes (glycemia > 8 mmol/L or 144 mg/dL ) Administration of any anticancer therapy within 1 month prior to study entry. Patients with complete resection of the tumor lesion(s). Administration of another investigational medicinal product within 30 days or within 5 terminal elimination half-lives of a previous investigational medicinal product, whichever is longer, prior to study entry. Current greater than grade 2 toxicity from any reason, per US-NCI Common Terminology Criteria for Adverse Events v5.0 (CTCAE version 5.0) except if tumor-related. Pregnant or breast-feeding women. Concomitant prohibited treatment which may interfere with [68Ga]Ga-PTF PET/CT imaging (e.g., systemic corticosteroids) and/or [18F]FDG PET/CT imaging administered within the last 1 month prior to study start. 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). Body weight of less than 48 kg.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [68Ga]Ga-PTF PET/CT<br>150 (+/-50) MBq [68Ga]Ga-PTF will be administered intravenously and PET/CT will be performed | Drug: [68Ga]Ga-PentixaFor<br>* [68Ga]Ga-PTF i.v. injection<br>* Other names: [68Ga]Ga-PTF;|
| Active Comparator: [18F]FDG PET/CT<br>[18F]FDG will be administered once intravenously according to the SMPC and PET/CT will be performed | Drug: [18F]Fluorodeoxyglucose<br>* [18F]FDG i.v. injection.<br>* Other names: [18F]FDG;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of [68Ga]Ga-PTF PET/CT imaging vs. [18F]FDG PET/CT imaging in tumor detection |  | Through study completion, an average of 6 months | 
| Specificity of [68Ga]Ga-PTF PET/CT imaging vs. [18F]FDG PET/CT imaging in tumor detection |  | Through study completion, an average of 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with additional or less tumoral lesions detected by [68Ga]Ga-PTF PET/CT imaging compared to [18F]FDG PET/CT imaging |  | Through study completion, an average of 6 months | 
| Inter-reader and intra-reader agreement for tumor detection of each PET/CT imaging agent on a lesion-basis and patient-basis |  | Through study completion, an average of 6 months | 
| Reproducibility of [68Ga]Ga-PTF PET/CT imaging (reproducibility group) |  | Through study completion, an average of 6 months | 
| Maximum standardized uptake value (SUVmax), SUVpeak and SUV mean of each PET/CT imaging agent |  | Through study completion, an average of 6 months | 
| Target-to-background ratio (TBR) of each PET/CT imaging agent |  | Through study completion, an average of 6 months | 
| Contrast-to-noise ratio (CNR) of each PET/CT imaging agent |  | Through study completion, an average of 6 months | 
| Signal-to-noise ratio (CNR) of each PET/CT imaging agent |  | Through study completion, an average of 6 months | 
| Frequency and Severity of Adverse Events for each PET/CT imaging agent |  | Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent | 
| Frequency and kind of adverse effects present at the injection site | The safety and tolerability for each PET/CT imaging agent will be evaluated by the assessment of the injection site status (which kind of adverse effects have appeared) after the injection of each PET/CT imaging compound | 2-3 hours after injection of each PET/CT imaging agent | 
| Clinical significance of abnormal results during physical examination | The safety and tolerability for each PET/CT imaging agent will be evaluated by the assessment of physical examination findings | Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent | 
| Blood pressure (systolic and diastolic) | The safety and tolerability for each PET/CT imaging agent will be evaluated by the assessment of blood pressure (systolic and diastolic) | Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent | 
| Heart or pulse rate | The safety and tolerability for each PET/CT imaging agent will be evaluated by the assessment of heart or pulse rate | Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent | 
| RR interval findings/abnormalities | The safety and tolerability for each PET/CT imaging agent will be evaluated by the assessment of findings/abnormalities in the RR interval | Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent | 
| PQ interval findings/abnormalities | The safety and tolerability for each PET/CT imaging agent will be evaluated by the assessment of PQ interval findings/abnormalities | Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent | 
| QRS complex findings/abnormalities | The safety and tolerability for each PET/CT imaging agent will be evaluated by the assessment of QRS complex findings/abnormalities | Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent | 
| QT interval findings/abnormalities | The safety and tolerability for each PET/CT imaging agent will be evaluated by the assessment of QT interval findings/abnormalities | Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent | 
| QTc interval findings/abnormalities | The safety and tolerability for each PET/CT imaging agent will be evaluated by the assessment of QTc interval findings/abnormalities | Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent | 
| Weight | The safety and tolerability for each PET/CT imaging agent will be evaluated by the assessment of patient weight | Prior injection of each PET/CT imaging agent and after injection of each PET/CT imaging agent | 
| Positive and negative predictive values (PPV, NPV) of each PET/CT imaging agent to detect tumor on a patient-basis and lesion-basis |  | Through study completion, an average of 6 months | 
| Detection rate of each PET/CT imaging agent to detect tumor on a patient-basis and lesion-basis confirmed by SoT or surrogate SoT |  | Through study completion, an average of 6 months | 
| Proportion of patients with additional or less lesions detected by each PET/CT imaging agent ([68Ga]Ga-PTF and [18F]FDG) compared to pre-PET conventional staging as assessed by questionnaires completed by the referring physicians |  | Through study completion, an average of 6 months | 
| Proportion of patients with a change in intended patient management due to additional or less lesions detected by each PET/CT imaging agent ([68Ga]Ga-PTF and [18F]FDG) as assessed by questionnaires completed by the referring physicians |  | Through study completion, an average of 6 months | 
| Proportion of patients with additional or less lesions detected by each PET/CT imaging agent ([68Ga]Ga-PTF and [18F]FDG) compared to pre-PET conventional staging as assessed by questionnaires completed by an Independent Committee |  | Through study completion, an average of 6 months | 
| Inter-observer agreement of local and central assessment in terms of staging |  | Through study completion, an average of 6 months | 
| Proportion of patients with nodal MZL with additional or less lesions detected by each PET/CT imaging agent ([68Ga]Ga-PTF and [18F]FDG) compared to pre-PET conventional staging as assessed by questionnaires completed by the referring physicians |  | Through study completion, an average of 6 months | 
| Proportion of patients with extranodal MZL with additional or less lesions detected by each PET/CT imaging agent ([68Ga]Ga-PTF and [18F]FDG) compared to pre-PET conventional staging as assessed by questionnaires completed by the referring physicians |  | Through study completion, an average of 6 months | 
| Proportion of patients with splenic MZL with additional or less lesions detected by each PET/CT imaging agent ([68Ga]Ga-PTF and [18F]FDG) compared to pre-PET conventional staging as assessed by questionnaires completed by the referring physicians |  | Through study completion, an average of 6 months | 
| Proportion of patients with nodal MZL with a change in intended patient management due to additional or less lesions detected by each PET/CT imaging agent ([68Ga]Ga-PTF and [18F]FDG) as assessed by questionnaires completed by the referring physicians |  | Through study completion, an average of 6 months | 
| Proportion of patients with extranodal MZL with a change in intended patient management due to additional or less lesions detected by each PET/CT imaging agent ([68Ga]Ga-PTF;[18F]FDG) as assessed by questionnaires completed by the referring physicians |  | Through study completion, an average of 6 months | 
| Proportion of patients with splenic MZL with a change in intended patient management due to additional or less lesions detected by each PET/CT imaging agent ([68Ga]Ga-PTF and [18F]FDG) as assessed by questionnaires completed by the referring physicians |  | Through study completion, an average of 6 months | 
| Diagnostic performance, consisting of sensitivity and specificity, of each PET/CT imaging agent in tumor detection on a region-basis (eyes, ears, nose, throat, liver, spleen, gastrointestinal tract, bone marrow) confirmed by SoT or surrogate SoT |  | Through study completion, an average of 6 months | 
| Sensitivity of each PET/CT imaging agent in tumor detection on a patient-basis confirmed by SoT or surrogate SoT |  | Through study completion, an average of 6 months |