Clinical trial NCT05222269: [68Ga]Ga-PentixaFor PET Imaging in CNS Lymphoma Patients
Official title: A Prospective, International, Multi-centre, Open-label, Single-arm Phase II Study Investigating the Predictive Value of [68Ga]Ga PentixaFor PET Imaging in Primary and Isolated Secondary CNS Lymphoma Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: CNS Lymphoma
Lead sponsor: Pentixapharm AG
Sponsor class: INDUSTRY
First posted: 2022-02-03
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: This will be an open, single-arm, international, multicentre, phase II imaging study to assess the predictive value of \[68Ga\]Ga PentixaFor PET imaging in primary and isolated secondary central nervous system lymphoma (CNSL) patients scheduled to undergo induction chemotherapy.


Eligibility criteria: Inclusion Criteria:

1. Written informed consent obtained according to international guidelines and local laws by patient (or legally acceptable representative, if the patient is temporarily legally not competent owing to his/her disease). \[Note: No invasive study-specific procedures may be carried out until this consent has been given.\]
2. Patient aged 18 years or above (either sex).
3. Histologically confirmed primary or secondary CNSL based on cytology/flow cytometry of cerebrospinal fluid (CSF) or brain biopsy.
4. Disease exclusively located in the CNS (primary CNSL or secondary CNSL with isolated CNS relapse). Subjects who had undergone allogeneic stem cell transplant \> 12 months prior to first dose of study drug, have no evidence of active graft versus host disease, and are not on systemic immunosuppressive therapy are allowed to participate in the study.
5. At least one measurable parenchymal lesion. \[Note: parenchymal CNSL is a "must", and additional locations such as leptomeningeal disease are permitted.\]
6. Previously untreated CNS disease. \[Note: Previous or ongoing steroid treatment is permitted. Prophylaxis chemotherapy is not necessary, as induction chemotherapy will start within 72 hours after PTF-PET.\]
7. At least one morphologically measurable lesion according to the IPCG criteria (Appendix 1).
8. Patients scheduled to undergo induction chemotherapy based on one of the following:

   High-dose methotrexate (HD-MTX)-based chemotherapy, ICE/DeVIC or High-dose cytarabine (HD-AraC)-based chemotherapy.
9. ECOG performance status ≤ 2 for patients aged ≥65 years; ECOG performance status ≤ 3 for patients aged \<65 years.
10. Life expectancy of at least 3 months, as estimated by the investigator.
11. For women of child-bearing potential: negative pregnancy test.
12. For sexually active female patients of child-bearing potential: The patient agrees to take adequate contraceptive measures during study participation and also agrees to continue use of this method for the duration of the study and for 6 months after the last dose of PTF.
13. For male patients whose partner is of child-bearing potential: The patient is willing to ensure that he and his partner use effective contraception during the study and for 6 months after the last dose of PTF.

Exclusion Criteria:

1. Known hypersensitivity to \[68Ga\]Ga-PentixaFor or its components.
2. Contraindication for contrast-enhanced MRI as set out in the relevant institutional guidelines (e.g., pacemaker, defibrillator, aneurysm clip, metal in the body, renal insufficiency, severe claustrophobia etc.).
3. Contraindication for the use of gadolinium contrast for MRI.
4. Contraindication for PET according to institutional guidelines (weight-based, e.g. weight \> 180 kg).
5. Inability to lie still for the entire imaging time.
6. Systemic lymphoma manifestation (outside the CNS).
7. Presence of active infection at screening or history of serious infection within the previous 6 weeks (except HIV infection: patients with HIV-associated primary CNSL are considered eligible).
8. Administration of another investigational medicinal product within the 30 days (or 5 excretion half-lives, whichever period is the longer) before first treatment with PTF.

   \[Note: Re screening may be performed to accept washout of prior agents.\]
9. Current toxicity of Grade \>2 from previous standard or investigational therapies (grade according to the NCI Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE 5.0).
10. For female patients: Pregnancy (existing or intended) or breast-feeding.
11. Renal impairment: Both of the following:

    Estimated glomerular filtration rate (eGFR) \< 30 ml/min/1.73 m2 Creatinine clearance \< 60 ml/min
12. Hepatic impairment: Both of the following:

    Aspartate aminotransferase (AST) \> 3x upper limit of normal Alanine aminotransferase (ALT) \> 3x upper limit of normal
13. Presence of any unstable systemic disease (including, but not limited to, active infection, uncontrolled hypertension, unstable angina, congestive heart failure, serious cardiac arrhythmia requiring medication, hepatic, renal or metabolic disease.
14. Presence of psychiatric disease, alcohol abuse or any other medical condition(s) that, in the opinion of the investigator, makes the patient unable to comply with study procedures and visits.
15. Patient weight ≤ 48 kg

Primary outcomes:
measure: Negative predictive value (NPV) of interim 68Ga-PTF-PET (after 6 ± 2 weeks of induction chemotherapy) for progression-free survival (PFS)
timeFrame: after 6 +/-2 weeks of induction chemotherapy (interim examination) up to 12 months after induction chemotherapy completion (end of follow-up period)
Secondary outcomes:
measure: Positive predictive value (PPV) of interim 68Ga-PTF PET (after 6 ± 2 weeks of induction chemotherapy) for PFS
timeFrame: after 6 +/-2 weeks of induction chemotherapy (interim examination) up to 12 months after induction chemotherapy completion (end of follow-up period)
measure: Frequency and severity of AEs
timeFrame: up to 6 months
measure: Predictive values of 68Ga-PTF PET at the end of induction chemotherapy for PFS
timeFrame: end of induction chemotherapy up to 12 months after induction chemotherapy completion
measure: Predictive values of 68Ga-PTF PET at interim examination (after 6 ± 2 weeks of induction chemotherapy) and end-of-chemotherapy-treatment for complete response (CR)
timeFrame: after 6 +/-2 weeks of induction chemotherapy (interim examination) up to 12 months after induction chemotherapy completion (end of follow-up period)
measure: Maximum standardized uptake value (SUVmax), SUVpeak and SUV mean
timeFrame: after pretreatment examination up to 12 months after induction chemotherapy completion (end of follow-up period)
measure: Maximum tumour-to background ratio (TBRmax) and TBRmean
timeFrame: after pretreatment examination up to 12 months after induction chemotherapy completion (end of follow-up period)
measure: Metabolic tumour volume (MTV)
timeFrame: after pretreatment examination up to 12 months after induction chemotherapy completion (end of follow-up period)
measure: Maximum standardized uptake value (SUVmax), SUVpeak and SUV mean
timeFrame: after 6 +/-2 weeks of induction chemotherapy (interim examination) up to 12 months after induction chemotherapy completion (end of follow-up period)
measure: Maximum tumour-to background ratio (TBRmax) and TBRmean
timeFrame: after 6 +/-2 weeks of induction chemotherapy (interim examination) up to 12 months after induction chemotherapy completion (end of follow-up period)
measure: Metabolic tumour volume (MTV)
timeFrame: after 6 +/-2 weeks of induction chemotherapy (interim examination) up to 12 months after induction chemotherapy completion (end of follow-up period)
measure: Predictive values of changes between pre-treatment and interim 68Ga-PTF PET imaging parameters for PFS
timeFrame: From visit 2 (first 68Ga-PTF PET) up to 12 months after induction chemotherapy completion
measure: Sensitivity of pre-treatment 68Ga-PTF PET for CXCR4-positivity
timeFrame: up to 12 months after induction chemotherapy completion
measure: Concordance in the classification as CNSL-suspect ('yes'/'no') by 68Ga-PTF PET and MRI at baseline, on a patient level
timeFrame: after Visit 4 (after 6 +/-2 weeks of induction chemotherapy)
measure: Comparison of lesion numbers categorised as CNSL-suspect by 68Ga-PTF PET and MRI at baseline
timeFrame: after Visit 4 (after 6 +/-2 weeks of induction chemotherapy)
measure: Observer agreement of 68Ga-PTF PET (inter- and intra-reader agreement)
timeFrame: through study completion, an average of 6 months
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: University Hospital Aalborg
city: Nantes
country: France
facility: University Hospital CHU Nantes
Study officials:
References: