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

Marginal Zone Lymphoma Clinical Trial

— LYMFOR  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06125028
• Other study ID #: PTF301
• Status: Recruiting
• Phase: Phase 3
• Start date: June 2024
• Est. completion date: June 15, 2025

Study information

• Verified date: May 2024
• Source: Pentixapharm AG
• Contact: Pinyada Redlich
• Phone: 00491724274560
• Email: pinyada.redlich[@]pentixapharm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 148
• Est. completion date: June 15, 2025
• Est. primary completion date: June 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

1. Signed informed consent form (ICF) from the patient.

2. Patients of either gender, aged = 18 years.

3. 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).

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:

• 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.

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:

1. Known hypersensitivity to any active pharmaceutical agent or constituent of the [68Ga]Ga-PTF and/or [18F]FDG product.

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 or [18F]FDG PET/CT imaging.

4. Patients presenting uncontrolled diabetes (glycemia > 8 mmol/L or 144 mg/dL )

5. Administration of any anticancer therapy within 1 month prior to study entry.

6. Patients with complete resection of the tumor lesion(s).

7. 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.

8. 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.

9. Pregnant or breast-feeding women.

10. 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.

11. 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).

12. Body weight of less than 48 kg.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Marginal Zone Lymphoma

Intervention

Drug:
• [68Ga]Ga-PentixaFor
[68Ga]Ga-PTF i.v. injection
• [18F]Fluorodeoxyglucose
[18F]FDG i.v. injection.

Locations

Country	Name	City	State
Spain	Clinica Universidad de Navarra	Pamplona	Navarra

Sponsors (2)

Lead Sponsor	Collaborator
Pentixapharm AG	Pivotal S.L.

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Sensitivity of [68Ga]Ga-PTF PET/CT imaging in detecting CXCR4 overexpressing tissue confirmed by a CXCR4 SoT (CXCR4 IHC)	Sensitivity of [68Ga]Ga-PTF PET/CT imaging in detecting CXCR4 overexpressing tissue will be analyzed on a lesion-basis and will be confirmed by a CXCR4 SoT (CXCR4 IHC)	Through study completion, an average of 6 months
Other	Specificity of [68Ga]Ga-PTF PET/CT imaging in detecting CXCR4 overexpressing tissue	Specificity of [68Ga]Ga-PTF PET/CT imaging in detecting CXCR4 overexpressing tissue will be analyzed on a lesion-basis and will be confirmed by a CXCR4 SoT (CXCR4 IHC)	Through study completion, an average of 6 months
Other	Receiver-operating-characteristic (ROC) curve analysis		Through study completion, an average of 6 months
Other	Determination of the area under the curve (AUC)		Through study completion, an average of 6 months
Other	Correlation of [68Ga]Ga-PTF uptake in PET and CXCR4 overexpression by IHC		Through study completion, an average of 6 months
Other	Correlation of the Ki-67 proliferation index with CXCR4 overexpression and with SUVmean on a lesion-basis		Through study completion, an average of 6 months
Other	Correlation of the Ki-67 proliferation index with CXCR4 overexpression and with SUVmax on a lesion-basis		Through study completion, an average of 6 months
Other	Rate of non-tumoral CXCR4-positive and CXCR4-negative lesions found in the [68Ga]Ga-PTF PET/CT imaging		Through study completion, an average of 6 months
Other	Percentage of patients with within-patient discordant lesions in terms of CXCR4 expression		Through study completion, an average of 6 months
Other	Positive predictive value (PPV) of [68Ga]Ga-PTF PET/CT imaging for detection of CXCR4 overexpressing tissue		Through study completion, an average of 6 months
Other	Negative predictive value (NPV) of [68Ga]Ga-PTF PET/CT imaging for detection of CXCR4 overexpressing tissue		Through study completion, an average of 6 months
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	Inter-observer agreement of local and central assessment in terms of staging		Through study completion, an average of 6 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Reproducibility of [68Ga]Ga-PTF PET/CT imaging (reproducibility group)		Through study completion, an average of 6 months
Secondary	Maximum standardized uptake value (SUVmax), SUVpeak and SUV mean of each PET/CT imaging agent		Through study completion, an average of 6 months
Secondary	Target-to-background ratio (TBR) of each PET/CT imaging agent		Through study completion, an average of 6 months
Secondary	Contrast-to-noise ratio (CNR) of each PET/CT imaging agent		Through study completion, an average of 6 months
Secondary	Signal-to-noise ratio (CNR) of each PET/CT imaging agent		Through study completion, an average of 6 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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